Oncology Research 26(2) Abstracts

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Oncology Research, Vol. 26, pp. 173-182, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14841698396865
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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CD103+ Cell Growth Factor Flt3L Enhances the Efficacy of Immune Checkpoint Blockades in Murine Glioblastoma Model

Xiaolin Miao,*1 Yiqi Chen,*1 Ke Hao,†1 Meiqin Zheng,‡ Bingyu Chen,† Kaiqiang Li,† Ying Wang,† Wei Zhang,§ Yu Zhang,§ Xiaozhou Mou,§ Shanshan Jiang,¶ and Zhen Wang‡§

*Eye Hospital of Wenzhou Medical University, Zhejiang, P.R. China
†Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Zhejiang, P.R. China
‡School of Laboratory Medicine and Life Science, Wenzhou Medical University, Zhejiang, P.R. China
§Clinical Research Institute, Zhejiang Provincial People’s Hospital, Zhejiang, P.R. China
¶Department of Gynecology, Zhejiang Provincial People’s Hospital, Zhejiang, P.R. China

Glioblastoma is a lethal disease featuring a high proliferation of tumor cells, excessive angiogenesis, and heavy drug resistance. The overall survival of glioblastoma patients has been dismal, even with an intensive standard of care. Recent advances in immune checkpoint blockades are changing the treatment of cancers. However, the efficacy of immune checkpoint blockades in glioblastoma is still unclear. Here we investigated the roles of CD103+
cells in regulating the effect of immune checkpoint blockades in glioblastoma mouse models. Our findings indicated that the murine glioblastoma model was not sensitive to immune checkpoint blockades. Flt3L, a growth factor for CD103+ cells, could significantly increase the number of CD103+ dendritic cells in the murine glioblastoma model and, thus, sensitize murine glioblastoma to immune checkpoint blockades. Downstream analysis indicated that the Flt3L and immune checkpoint blockade combination increased the number of tumor-infiltrating CD8+ cells, decreased immune checkpoint expression, and therefore enhanced the antitumor immune response in the murine glioblastoma model. These findings suggested that Flt3L could enhance the efficacy of immune checkpoint blockades in glioblastoma via expanding CD103+ dendritic cells and downstream antitumor immune response.

Key words: Glioblastoma; Immune checkpoints; Flt3L; CD103; Mouse model

1These authors provided equal contribution to this work.
Address correspondence to Shanshan Jiang, Department of Gynecology, Zhejiang Provincial People’s Hospital, 5th Floor, Tower III, 3 East Qingchuan Road, Hangzhou Medical University, Zhejiang, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Zhen Wang, School of Laboratory Medicine and Life Science, Wenzhou Medical University, University Town, Chashan, Wenzhou, Zhejiang, P.R. China and Clinical Research Institute, Zhejiang Provincial People’s Hospital, 158 Shangtang Road, Hangzhou, Zhejiang, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 183-189, 2018
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DOI: https://doi.org/10.3727/096504017X
14837020772250
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Knockdown of TACC3 Inhibits the Proliferation and Invasion of Human Renal Cell Carcinoma Cells

Feng Guo and Yaquan Liu

Department of Urology, The Central Hospital of Wuhan, Wuhan, P.R. China

Transforming acidic coiled-coil protein 3 (TACC3) is a member of the TACC family and plays an important role in regulating cell mitosis, transcription, and tumorigenesis. However, the expression pattern and roles of TACC3 in renal cell carcinoma (RCC) remain unclear. The aim of this study was to investigate the role of TACC3 in RCC. We demonstrated overexpression of TACC3 in human RCC cell lines at both RNA and protein levels. Moreover, knockdown of TACC3 repressed RCC cell proliferation, migration, and invasion in vitro. In addition, knockdown of TACC3 inactivated PI3K/Akt signaling in RCC cells. Furthermore, knockdown of TACC3 significantly reduced tumor growth in xenograft tumor-bearing mice. Taken together, our findings showed that TACC3 was increased in human RCC cell lines, and knockdown of TACC3 inhibited the ability of cell proliferation, migration, invasion, and tumorigenesis in vivo. Therefore, TACC3 may act as a therapeutic target for the treatment of human RCC.

Key words: Transforming acidic coiled-coil protein 3 (TACC3); Renal cell carcinoma (RCC); Proliferation; Invasion; PI3K/Akt pathway

Address correspondence to Yaquan Liu, Department of Urology, The Central Hospital of Wuhan, No. 16 of Gusaoshu Road, Wuhan 430014, P.R. China. Tel: +86-027-82811080; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 191-200, 2018
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DOI: https://doi.org/10.3727/096504017X
14965111926391
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Inhibition of Carbonic Anhydrase IX by Ureidosulfonamide Inhibitor U104 Reduces Prostate Cancer Cell Growth, But Does Not Modulate Daunorubicin or Cisplatin Cytotoxicity

Anne Riemann,* Antje Güttler,† Verena Haupt,* Henri Wichmann,† Sarah Reime,* Matthias Bache,† Dirk Vordermark,† and Oliver Thews*

*Julius-Bernstein-Institut für PhysiologieUniversität Halle-Wittenberg, Halle, Germany
Klinik und Poliklinik für StrahlentherapieUniversität Halle-Wittenberg, Halle, Germany

Carbonic anhydrase (CA) IX has emerged as a promising target for cancer therapy. It is highly upregulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment, which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells with regard to potential therapeutic implications. CA IX was upregulated by hypoxia as well as acidosis in prostate cancer cells. This induction did not modulate intracellular pH but led to extracellular acidification. Pharmacological inhibition of CA IX activity by U104 (SLC-0111) resulted in a reduction in tumor cell growth and an increase in apoptotic cell death. Intracellular pH was reduced under normoxic and even more so under hypoxic conditions when CA IX level was high. However, although intracellular pH regulation was disturbed, targeting CA IX in combination with daunorubicin or cisplatin did not intensify apoptotic tumor cell death. Hence, targeting CA IX in prostate cancer cells can lead to intracellular pH dysregulation and, consequently, can reduce cellular growth and elevate apoptotic cell death. Attenuation of extracellular acidification by blocking CA IX might additionally impede tumor progression and metastasis. However, no beneficial effect was seen when targeting CA IX in combination with chemotherapeutic drugs.

Key words: Carbonic anhydrase IX (CA IX); Acidosis; Intracellular pH; Cytotoxicity

Address correspondence to Anne Riemann, Julius-Bernstein-Institut für PhysiologieUniversität Halle-Wittenberg, Magdeburger Straße 6, 06112 Halle (Saale), Germany. Tel: +49-345-557-4434; Fax: +49-345-557-4019; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 201-208, 2018
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DOI: https://doi.org/10.3727/096504017X
14920318811749
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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The lncRNA CCAT1 Upregulates Proliferation and Invasion in Melanoma Cells via Suppressing miR-33a

Li Lv,* Jian-Qin Jia,* and Jin Chen†

*Department of Dermatology, Tianjin Hospital, Tianjin, P.R. China
†Department of Dermatology, Public Security Hospital, Tianjin, P.R. China

It is increasingly evident that various long noncoding RNAs (lncRNAs) participate in the tumorigenesis of multiple tumors, including melanoma. lncRNAs have been validated as oncogenic factors in various tumors; however, the potential regulatory mechanism of CCAT1 in melanoma is still unclear. The purpose of this study was to investigate the regulation of CCAT1 on melanoma genesis. The expression of CCAT1 in melanoma tissue and cell lines was measured using qRT-PCR. Interference oligonucleotide or mimic sequences were applied to up- or downregulate RNA expression. CCK-8 and colony formation assays were performed to detect the proliferation capability. Transwell assay was used to assess the migration and invasion capacities. Bioinformatics analysis was performed to predict the target miRNAs of CCAT1. Expression of CCAT1 was significantly upregulated in melanoma tissue and cell lines. CCAT1 knockdown observably suppressed the proliferation, migration, and invasion abilities. Bioinformatics analysis predicted that miR-33a acted as a target of CCAT1, which was confirmed by dual-luciferase reporter assay. CCAT1 knockdown reversed the tumor-promoting ability of the miR-33a inhibitor. CCAT1 acts as an oncogenic factor in the genesis of melanoma and exerts tumor-promoting roles via sponging miR-33a, providing a novel insight for competing endogenous RNA (ceRNA) in the tumorigenesis of melanoma.

Key words: Melanoma; CCAT1; miR-33a; Competing endogenous RNA (ceRNA)

Address correspondence to Li Lv, Department of Dermatology, Tianjin Hospital, No. 406 Liberation South Road, Hexi District, Tianjin 300211, P.R. China. Tel: +86-022-28332917; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 209-217, 2018
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DOI: https://doi.org/10.3727/096504017X
14944585873622
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Procaine Inhibits the Proliferation and Migration of Colon Cancer Cells Through Inactivation of the ERK/MAPK/FAK Pathways by Regulation of RhoA

Chang Li,* Shuohui Gao,* Xiaoping Li,Chang Li,and Lianjun Ma§

*Department of Gastrointestinal Surgery, China–Japan Union Hospital of Jilin University, Changchun, P.R. China
†Department of Pediatrics, The First Bethune Hospital of Jilin University, Changchun, P.R. China
‡Department of Cadre’s Ward, China–Japan Union Hospital of Jilin University, Changchun, P.R. China
§Endoscopy Center, China–Japan Union Hospital of Jilin University, Changchun, P.R. China

Colon cancer is one of the most lethal varieties of cancer. Chemotherapy remains as one of the principal treatment approaches for colon cancer. The anticancer activity of procaine (PCA), which is a local anesthetic drug, has been explored in different studies. In our study, we aimed to explore the anticancer effect of PCA on colon cancer and its underlying mechanism. The results showed that PCA significantly inhibited cell viability, increased the percentage of apoptotic cells, and decreased the expression level of RhoA in HCT116 cells in a dose-dependent manner (p < 0.05 or p < 0.01). Moreover, PCA increased the proportion of HCT116 cells in the G
1 phase as well as downregulated cyclin D1 and cyclin E expressions (p < 0.05). In addition, we found that PCA remarkably inhibited cell migration in HCT116 cells (p < 0.01). However, all these effects of PCA on cell proliferation, apoptosis, and migration were significantly reversed by PCA + pc-RhoA (p < 0.05 or p < 0.01). PCA also significantly decreased the levels of p-ERK, p-p38MAPK, and p-FAK, but PCA + pc-RhoA rescued these effects. Furthermore, the ERK inhibitor (PD098059), p38MAPK inhibitor (SB203580), and FAK inhibitor (Y15) reversed these results. These data indicate that PCA inhibited cell proliferation and migration but promoted apoptosis as well as inactivated the ERK/MAPK/FAK pathways by regulation of RhoA in HCT116 cells.

Key words: Colon cancer; HCT116; Procaine (PCA); RhoA; ERK/MAPK/FAK

Address correspondence to Chang Li, Department of Cadre’s Ward, China–Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Lianjun Ma, Endoscopy Center, China–Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 219-230, 2018
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DOI: https://doi.org/10.3727/096504017X
14944585873659
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Oncogenic Role of MicroRNA-30b-5p in Glioblastoma Through Targeting Proline-Rich Transmembrane Protein 2

Zhongjun Li,* Junxiu Guo,* Yujie Ma, Longbo Zhang,and Zhixiong Lin*

*Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, P.R. China
†Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China

MicroRNAs (miRs) have been found to play promoting or suppressive roles in different human cancers. However, the exact regulatory mechanism of miR-30b in glioblastoma remains unknown. Here we have shown that the expression of miR-30b is significantly increased in glioblastoma tissues and cell lines. Moreover, a high expression of miR-30b is significantly associated with a shorter survival time for glioblastoma patients. Knockdown of miR-30b caused a significant reduction in the proliferation, migration, and invasion of U87 and A172 cells. Proline-rich transmembrane protein 2 (PRRT2) was further identified as a novel target gene of miR-30b, and its protein expression is negatively regulated by miR-30b in U87 and A172 cells. Furthermore, PRRT2 is significantly downregulated in glioblastoma tissues and cell lines, and we found an inverse correlation between miR-30b and PRRT2 expression in glioblastoma tissues. In addition, inhibition of PRRT2 reversed the suppressive effect of miR-30b downregulation on the malignant phenotypes of U87 and A172 cells. Accordingly, we demonstrated that miR-30b promotes glioblastoma cell proliferation, migration, and invasion via targeting PRRT2. Therefore, miR-30b may be used as a promising therapeutic target for glioblastoma.

Key words: Glioblastoma; MicroRNA; Proline-rich transmembrane protein 2 (PRRT2); Oncogene; Tumor suppressor

Address correspondence to Zhixiong Lin, Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, #50 Xiangshanyikesong, Beijing 100093, P.R. China. Tel: +86-10-62856951; Fax: +86-10-62856951; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Longbo Zhang, Department of Neurosurgery, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, Hunan 410008, P.R. China. Tel: +86-731-89753739; Fax: +86-731-89753739; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 231-239, 2018
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DOI: https://doi.org/10.3727/096504017X
15051752095738
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Efficacy and Safety of Transcatheter Arterial Chemoembolization and Transcatheter Arterial Chemotherapy Infusion in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Xinyang Liu,*1 Zhichao Wang,*1 Zongwei Chen,†1 Longzi Liu,* Lijie Ma,* Liangqing Dong,* Zhao Zhang,* Shu Zhang,* Liuxiao Yang,* Jieyi Shi,* Jia Fan,*‡ Xiaoying Wang,* and QiangGao*‡

*Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P.R. China
†Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
‡State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, P.R. China

Hepatocellular carcinoma (HCC) is a worldwide health threat with increasing incidence and a high mortality rate. Most HCC patients are diagnosed at an advanced stage and are unable to undergo potential curative surgery. Transcatheter arterial chemoembolization (TACE) and transcatheter arterial chemotherapy infusion (TACI) are two of the main palliative treatments for advanced HCC patients. The clinical efficacy and safety of TACE and TACI are controversial. For this reason, we conducted a systematic review and meta-analysis to summarize the current evidence. We searched for randomized controlled trials (RCTs) and cohort studies that compared the clinical outcomes and adverse effects in HCC patients who received TACE or TACI treatments. The database search was performed and last updated on November 1, 2016. Overall survival and clinical response were compared using a hazard ratio (HR) with a 95% confidence interval (CI). A total of 11 clinical studies that included 13,090 patients were included based on the inclusion/exclusion criteria, of which 9 were cohort studies and 2 were RCTs. TACE was associated with a 23% lower hazard of death compared to TACI (pooled HR = 0.77, 95% CI = 0.67–0.88, p = 0.0002). Patients receiving TACE had a 28% higher disease control rate (DCR) and 162% higher objective response rate (ORR). Only the increase in ORR associated with TACE was statistically significant [DCR: odds ratio (OR) = 1.28, 95% CI = 0.35–4.64, p = 0.71; ORR: OR = 2.62, 95% CI = 1.33–5.15, p = 0.002]. TACE is associated with more favorable survival and response rate than TACI in patients with intermediate or advanced HCC.

Key words: Hepatocellular carcinoma (HCC); Transcatheter arterial chemoembolization (TACE); Transcatheter arterial chemotherapy infusion (TACI); Efficacy; Safety; Randomized clinical trials; Cohort studies; Meta-analysis

1These authors provided equal contribution to this work and are co-first authors.
Address correspondence to Dr./Prof. Qiang Gao, Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital Fudan University, No. 180 Feng Lin Road, Xuhui District, 200032 Shanghai, P.R. China. Tel: +86-21-64041990; Fax: +86-21-64041990; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Dr./Prof. Xiaoying Wang, Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital Fudan University, No. 180 Feng Lin Road, Xuhui District, 200032 Shanghai, P.R. China. Tel: +86-21-64041990; Fax: +86-21-64041990; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 241-247, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14953948675412
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Long Noncoding RNA CCAT2 Knockdown Suppresses Tumorous Progression by Sponging miR-424 in Epithelial Ovarian Cancer

Fu Hua,* Chang-Hua Li,* Xiao-Gang Chen,† and Xiao-Ping Liu*

*Department of Gynecology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, P.R. China
†Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, P.R. China

Epithelial ovarian cancer (EOC) is the one of most common gynecological malignant tumors with high mortality. A series of long noncoding RNAs (lncRNAs) have been validated to play a vital role in EOC tumorigenesis. Colon cancer-associated transcript 2 (CCAT2) has been verified as an oncogenic lncRNA in multiple tumors; however, the role of CCAT2 in EOC genesis is still unclear. The purpose of the present study was to probe the function of CCAT2 on EOC. Preliminary experiments found that CCAT2 expression was significantly upregulated in EOC tissues and cell lines compared to noncancerous tissue and cells. CCAT2 knockdown induced by interfering oligonucleotides could inhibit proliferation and promote apoptosis and induce cell cycle arrest at the G0/G1
phase. Bioinformatics analysis predicted that miR-424 targeted CCAT2, which was confirmed by luciferase reporter assay. Moreover, the miR-424 inhibitor rescued the tumorigenesis inhibition induced by CCAT2 knockdown. In summary, our findings illustrate that CCAT2 acts as competing endogenous RNA (ceRNA) or sponge via negatively targeting miR-424, providing a novel diagnostic marker and therapeutic target for EOC.

Key words: Epithelial ovarian cancer (EOC); Long noncoding RNAs (lncRNAs); CCAT2; miR-424

Address correspondence to Fu Hua, Department of Gynecology, Huai’an First People’s Hospital, Nanjing Medical University, No. 6 Beijing Road West, Huai’an, Jiangsu 223300, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 249-259, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14953948675430
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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MicroRNA-186 Suppresses Cell Proliferation and Metastasis Through Targeting Sentrin-Specific Protease 1 in Renal Cell Carcinoma

Dan Jiao,* Man Wu,Lei Ji,Feng Liu,§ and Yingying Liu§

*Department of Ultrasound, China–Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China
†Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin, P.R. China
‡Department of Cardiology, Changchun Central Hospital, Changchun, Jilin, P.R. China
§Department of Nephrology, China–Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China

Recent evidence suggests that dysregulation of microRNAs is associated with the development of multiple malignancies. miR-186 has been reported as a critical cancer regulator in several types of cancers. However, its functional significance and molecular mechanism underlying renal cell carcinoma (RCC) remain unknown. In this study, our results showed that miR-186 expression was dramatically downregulated in RCC tissues and cell lines compared to that in adjacent normal tissues and cell lines. Overexpression of miR-186 significantly inhibited cell growth, colony formation, and cell invasion; caused cell cycle arrest at the G0/G1
phase; and induced cell apoptosis as detected by MTT, colony formation, Transwellassay, and flow cytometry assays in RCC cells. In addition, inhibition of miR-186 expression promoted RCC cell proliferation, invasion, and cell cycle progression and reduced apoptosis. Bioinformatics analysis and luciferase reporter assay confirmed that the 3′-UTR of sentrin-specific protease 1 (SENP1) was a direct target of miR-186. A remarkably reverse correlation was observed between miR-186 and SENP1 mRNA in RCC tissues. Furthermore, immunohistochemical staining revealed that SENP1 was positively expressed in RCC specimens. Restoration of SENP1 expression could partially abrogate the inhibitory effect of miR-186 overexpression on RCC cell proliferation through activating NF-κB signaling and its downstream proteins. These data demonstrated that miR-186 acted as a novel tumor suppressor and potential therapeutic biomarker in the progression of RCC by directly targeting SENP1.

Key words: Renal cell carcinoma (RCC); miR-186; SENP1; Proliferation; Tumor suppressor

Address correspondence to Yingying Liu, Department of Nephrology, China–Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033 Jilin, P.R. China. Tel: +86 0431-84995999; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 261-268, 2018
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DOI: https://doi.org/10.3727/096504017X
15031557924132
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Long Noncoding RNA PlncRNA-1 Promotes Colorectal Cancer Cell Progression by Regulating the PI3K/Akt Signaling Pathway

Wei Song,* Jia-Zhuan Mei,† and Mingzhi Zhang‡

*The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
†Department of Oncology, The People’s Hospital of Zhengzhou, Zhengzhou, Henan, P.R. China
‡Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China

Accumulating evidence has indicated that long noncoding RNA (lncRNA) PlncRNA-1 plays an important regulatory role in cancers. However, the expression and biological functions of PlncRNA-1 in colorectal cancer (CRC) are still unclear. In the present study, we determined the expression of PlncRNA-1 in CRC and explored the function of PlncRNA-1 on CRC cell progression. The results showed that PlncRNA-1 was significantly increased in CRC tissues and cell lines; high PlncRNA-1 expression was associated with depth of invasion, lymph node metastasis, and TNM stage of CRC patients. Kaplan–Meier curve analysis showed that patients with high PlncRNA-1 expression had a poor overall survival. PlncRNA-1 knockdown remarkably reduced cell proliferation, migration, and invasion and promoted cell apoptosis in vitro. In vivo xenograft experiments showed that PlncRNA-1 inhibition significantly suppressed tumor growth. Finally, we used an agonist (740Y-P) of the PI3K/Akt signaling pathway; function assays showed that PlncRNA-1 exerted its effects by targeting the PI3K/Akt signaling pathway in CRC. Taken together, our data suggested that PlncRNA-1 might act as an oncogene in CRC progression and serve as a potential biomarker and therapeutic target for the treatment of CRC.

Key words: Long noncoding RNAs (lncRNAs); PlncRNA-1; Colorectal cancer (CRC); Progression; PI3K/Akt

Address correspondence to Mingzhi Zhang, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, 27 District, Zhengzhou 450000, Henan Province, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 269-276, 2018
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DOI: https://doi.org/10.3727/096504017X
15075967560980
E-ISSN 1555-3906
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Non-SMC Condensin I Complex, Subunit G (NCAPG) is a Novel Mitotic Gene Required for Hepatocellular Cancer Cell Proliferation and Migration

Qun Zhang, Ruixia Su, Chun Shan, Chao Gao, and Pei Wu

Division of Infectious Diseases, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu Province, P.R. China

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Currently, only chemoembolization and sorafenib have shown survival benefits for advanced HCC. There are major unmet needs in HCC management and the discovery of new therapeutic targets. Here we identified NCAPG (non-SMC condensin I complex, subunit G) as a novel mitotic gene required for HCC cell proliferation and migration through siRNA knockdown of a panel of novel overexpressed genes in HCC based on The Cancer Genome Atlas (TCGA) dataset. We found that knockdown of NCAPG induces HCC cell mitosis and inhibits cell growth, proliferation, and migration in vitro. Tetracycline-inducible shRNA knockdown of NCAPG inhibits tumor growth of HCC cells in vivo. Moreover, overexpression of NCAPG in clinical HCC samples was associated with recurrence and survival of patients. The overexpression of NCAPG was significantly correlated with the overexpression of CCNB1 (G2/mitotic-specific cyclin B1), a regulatory protein involved in mitosis. Therefore, NCAPG may provide a promising novel therapeutic target for the treatment of advanced HCC in the future.

Key words: Hepatocellular carcinoma (HCC); NCAPG; Proliferation; Migration

Address correspondence to Dr. Qun Zhang, Division of Infectious Diseases, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Nanjing, Jiangsu Province 210009, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 277-287, 2018
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DOI: https://doi.org/10.3727/096504017X
15079846743590
E-ISSN 1555-3906
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Long-Term Use of Nimotuzumab in Combination With Intensity-Modulated Radiotherapy and Chemotherapy in the Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma: Experience of a Single Institution

Wang Fangzheng,*†1 Jiang Chuner,‡1 Ye Zhiming,*† Liu Tongxin,*† Yan Fengqin,*† Wang Lei,*† Li Bin,*† Hu Fujun,*† Chen Ming,*† Qin Weifeng,*† and Fu Zhenfu*†

*Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhejiang, Hangzhou, P.R. China
†Zhejiang Key Laboratory of Radiation Oncology, Zhejiang, Hangzhou, P.R. China
‡Department of Breast Surgery, Zhejiang Cancer Hospital, Zhejiang, Hangzhou, P.R. China

In this retrospective review of a single institution’s experience, the efficacy and safety of the long-term use of nimotuzumab in combination with intensity-modulated radiotherapy (IMRT) and chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC) were studied. Between August 2008 and March 2014, 39 newly diagnosed patients with stages III–IV NPC were treated with IMRT, chemotherapy, and nimotuzumab. Twenty patients were diagnosed with stage III (51.3%), 14 with stage IVA (35.9%), and 5 with stage IVB (12.8%) disease. All patients received at least one cycle of cisplatin-based induction chemotherapy followed by IMRT and more than nine cycles of nimotuzumab at 200 mg/week. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group. Accumulated survival was calculated according to the Kaplan–Meier method. The log-rank test was used to compare survival differences. With a median follow-up of 46 months (range, 22–86 months), the estimated 3-year local recurrence-free, regional recurrence-free, distant metastasis-free, progression failure-free, and overall survival rates were 92.1%, 89.7%, 82.5%, 77.6%, and 86.8%, respectively. Univariate analysis showed that clinical stage and the cycle of induction chemotherapy were related with prognosis. The median cycle for the addition of nimotuzumab was 12 weeks. Grade 3 radiation-induced mucositis was observed in 15.8% of the treated patients. No skin rash or infusion reaction was observed, which is distinctly different from what was reported in patients treated with nimotuzumab. The major toxicities observed were grades I–II mucositis and leukocytopenia. Long-term use of nimotuzumab plus IMRT showed promising outcomes in terms of locoregional control and survival, without increasing the incidence of radiation-related toxicities in patients.

Key words: Nasopharyngeal carcinoma (NPC); Intensity-modulated radiotherapy (IMRT); Nimotuzumab; Prognosis

1These authors provided equal contribution to this work.
Address correspondence to Qin Weifeng, Department of Radiation Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Zhejiang, Hangzhou 310022, P.R. China. Tel: 86-571-88128192; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Fu Zhenfu, Department of Radiation Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Zhejiang, Hangzhou 310022, P.R. China. Tel: 86-57188128195; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 289-296, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15009404458675
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Long Noncoding RNA NEAT1 Promotes Proliferation and Invasion via Targeting miR-181a-5p in Non-Small Cell Lung Cancer

ShiDong Li,*† JiaMei Yang,† Yubing Xia,‡ QingXia Fan,* and Kun-peng Yang§

*Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
†Department of Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
‡Department of Radiotherapy, Kaifeng Cancer Hospital, Kaifeng, P.R. China
§Department of Thoracic Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China

Long noncoding RNAs (lncRNAs) have been implicated in various biological processes and pathological conditions, including tumorigenesis. However, the exact roles of NEAT1 and its underlying mechanisms in non-small cell lung cancer (NSCLC) remain largely unclear. In the present study, lncRNA NEAT1 was detected to be significantly upregulated in NSCLC tissues and closely associated with advanced TNM stages, lymph node metastasis, distant metastasis, and poor prognosis. Further experiments revealed that lncRNA NEAT1 silencing inhibited cell proliferation and invasion in vitro. In addition, mechanistic analysis showed that lncRNA NEAT1 upregulated the miR-181a-5p-targeted gene HMGB2 through acting as a competitive “sponge” of miR-181-a-5p. In conclusion, our study suggested that lncRNA NEAT1 plays an oncogenic role in NSCLC progression and provides potential mechanisms by which lncRNA NEAT1 contributes to this disease.

Key words: Non-small cell lung cancer (NSCLC); Long noncoding RNAs (lncRNAs); Nuclear-enriched abundant transcript 1 (NEAT1); miR-181a-5p; HMGB2

Address correspondence to QingXia Fan, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jian She East Road, Erqi District, Zhengzhou 450052, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 297-305, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14980882803151
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Long Noncoding RNA MEG3 Inhibits Cell Proliferation and Metastasis in Chronic Myeloid Leukemia via Targeting miR-184

Jingdong Li, Youmei ZiWanling Wang, and Yan Li

Department of Hematology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, P.R. China

Maternally expressed gene 3 (MEG3), a long noncoding RNA, has been reported to be associated with the pathogenesis of multiple malignancies. However, little is known regarding the role of MEG3 in leukemia. In this study, we found that the expression of MEG3 was decreased in leukemia patients and cell lines and has potential to be considered as a biomarker for leukemia. In addition, overexpression of MEG3 inhibited cell proliferation and invasion in vitro and in vivo. Moreover, a potential bonding site between miR-184 and MEG3 was predicted, and low expression of miR-184 was found in leukemia patients and cell lines. In vitro loss and gain of function showed that overexpression of MEG3 significantly decreased the expression of miR-184, and MEG3 knockdown markedly increased it. Furthermore, our results showed that MEG3 interacted with miR-184 and subsequently mitigated the proliferation and invasion of leukemia cells by downregulating related proteins. In conclusion, our study has identified a novel pathway through which MEG3 acts as a tumor suppressor in leukemia at the level of miRNAs and provided a molecular basis for potential applications of MEG3 in the prognosis and treatment of leukemia.

Key words: Long noncoding RNAs (lncRNAs); Maternally expressed gene 3 (MEG3); miR-184; Leukemia

Address correspondence to Jingdong Li, Department of Hematology, the First Affiliated Hospital of Xinxiang Medical University, No. 88 Jiankang Road, Weihui County, Xinxiang, Henan 453100, P.R. China. Tel: (+86) 0373-4403432; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 307-313, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15088061795756
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Knockdown of Long Noncoding RNA LUCAT1 Inhibits Cell Viability and Invasion by Regulating miR-375 in Glioma

Yan-Sheng Gao,* Xian-Zhi Liu,† Yong-Gang Zhang,* Xian-Jin Liu,* and Ling-Zhen Li‡

*Department of Neurosurgery, Zhumadian Central Hospital, Zhumadian, Henan, P.R. China
†Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
‡Department of Neurology, Zhumadian Central Hospital, Zhumadian, Henan, P.R. China

Recently, long noncoding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in several cancers, including glioma. Here we focused on lncRNA LUCAT1 on the progression of glioma. qRT-PCR was used to determine the expression of LUCAT1 and miR-375 in glioma tissues and cells. MTT and Transwell invasion assays were performed to determine the function of LUCAT1 in glioma progression. The bioinformatics tool DIANA was used to predict the targets of LUCAT1. Pearson’s correlation analysis was performed to explore the correlation between LUCAT1 and miR-375. In the present study, we showed that LUCAT1 was substantially upregulated in glioma tissues and cells. LUCAT1 inhibition significantly suppressed the proliferation and invasion of glioma cells. Subsequently, DIANA showed that miR-375 was predicted to contain the complementary binding sites to LUCAT1. Luciferase reporter assay showed that miR-375 directly targeted LUCAT1. In addition, we found that miR-375 was downregulated in glioma tissues and negatively correlated with LUCAT1 expression in glioma tissues. Furthermore, the results showed that miR-375 could rescue the function of LUCAT1 in glioma progression. The lncRNA LUCAT1 was critical for the proliferation and invasion of glioma cells by regulating miR-375. Our findings indicated that LUCAT1 might offer a potential novel therapeutic target for the treatment of glioma.

Key words: Long noncoding RNAs (lncRNAs); LUCAT1; miR-375; Glioma; Progression

Address correspondence to Yan-Sheng Gao, Department of Neurosurgery, Zhumadian Central Hospital, No. 747 Zhonghua Road, Zhumadian, 463000 Henan, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 315-322, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15067856789781
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA-433 Represses Proliferation and Invasion of Colon Cancer Cells by Targeting Homeobox A1

Heming Li,*1 Junfeng Li,*1 Taisheng Yang,* Shuwen Lin,† and Heng Li‡

*Emergency Department, 5th Hospital of Dongguan City, Dongguan, P.R. China
†Hepatobiliary Surgery Department, 5th Hospital of Dongguan City, Dongguan, P.R. China
‡Cardiovascular Department, TungWah Hospital of Sun-Yat Sen University, Donggguan, P.R. China

The aberrant expression of miR-433 has been validated in some types of cancers. However, the expression profile and the biological function of miR-433 on colon cancer are still elusive. This study was designed to investigate the function of miR-433 on the proliferation and invasion of colon cancer cells. We detected the expression of miR-433 in colon cancer tissues, adjacent normal tissues, and cell lines. CCK8 and Transwell assays were performed to explore the impact of miR-433 on colon cancer cell proliferation and invasion. The luciferase reporter assay was applied to identify the direct target of miR-433. The results demonstrated that miR-433 was downregulated in colon cancer tissues and cell lines when compared with the control. Overexpression of miR-433 significantly suppressed the ability of colon cancer cell proliferation and invasion, whereas knockdown of miR-433 remarkably enhanced cell proliferation and invasion. Homeobox A1 (HOXA1) was identified as a target of miR-433, and it mediated the functions of miR-433 on colon cancer cells. To conclude, we revealed that miR-433 was downregulated in colon cancer, and it inhibited colon cancer cell proliferation and invasion by directly targeting HOXA1.

Key words: miR-433; Colon cancer; Proliferation; Invasion; Homeobox A1 (HOXA1)

1These authors provided equal contribution to this work.
Address correspondence to Heng Li, Cardiovascular Department, TungWah Hospital of Sun-Yat Sen University, No. 1 West Road, Dong Cheng District, Dongguan, 523110 Guangdong, P.R. China. Tel: (86769)22676101; Fax: (86769)22676101; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 323-332, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14957929842972
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Nelfinavir and Ritonavir Kill Bladder Cancer Cells Synergistically by Inducing Endoplasmic Reticulum Stress

Akinori Sato, Takako Asano, Kazuki Okubo, Makoto Isono, and Tomohiko Asano

Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan

The human immunodeficiency virus (HIV) protease inhibitor nelfinavir acts against malignancies by inducing endoplasmic reticulum (ER) stress. The HIV protease inhibitor ritonavir, on the other hand, not only induces ER stress but also inhibits P-glycoprotein’s pump activity and thereby enhances the effects of its substrate drugs. We therefore postulated that ritonavir in combination with nelfinavir would kill bladder cancer cells effectively by inducing ER stress cooperatively and also enhancing nelfinavir’s effect. Nelfinavir was shown to be a P-glycoprotein substrate, and the combination of nelfinavir and ritonavir inhibited bladder cancer cell growth synergistically. It also suppressed colony formation significantly. The combination significantly increased the number of cells in the sub-G
1 fraction and also the number of annexin V+ cells, confirming robust apoptosis induction. The combination induced ER stress synergistically, as evidenced by the increased expression of glucose-regulated protein 78, ER-resident protein 44, and endoplasmic oxidoreductin-1-like protein. It also increased the expression of the mammalian target of rapamycin (mTOR) inhibitor AMP-activated protein kinase and caused dephosphorylation of S6 ribosomal protein, demonstrating that the combination also inhibited the mTOR pathway. We also found that the combination enhanced histone acetylation synergistically by decreasing the expression of HDACs 1, 3, and 6.

Key words: Nelfinavir; Ritonavir; Endoplasmic reticulum stress; Bladder cancer

Address correspondence to Akinori Sato, Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. Tel: +81-4-2995-1676; Fax: +81-4-2996-5210; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 333, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15187172557369
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Erratum

The following was originally published in Volume 25, Number 9, pages 1441–1451 (DOI: https://doi.org/10.3727/096504017X14926854178616). Information shown in Table 1 appeared incorrectly as (mM) ± SE in the column headings. The correct information should have appeared as (μM ± SE). The file available online has been corrected and the corrected Table 1 is shown below.

The Inhibitory Effects of HYDAMTIQ, a Novel PARP Inhibitor, on Growth in Human Tumor Cell Lines With Defective DNA Damage Response Pathways

Enrico Mini,* Ida Landini,* Laura Lucarini,† Andrea Lapucci,* Cristina Napoli,‡ Gabriele Perrone,* Renato Tassi,* Emanuela Masini,† Flavio Moroni,† and Stefania Nobili‡

*Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
†Department of NEUROFARBA, University of Florence, Florence, Italy
‡Department of Health Sciences, University of Florence, Florence, Italy

The poly(ADP-ribose) polymerase (PARP) enzymes play a key role in the regulation of cellular processes (e.g., DNA damage repair, genomic stability). It has been shown that PARP inhibitors (PARPIs) are selectively cytotoxic against cells having dysfunctions in genes involved in DNA repair mechanisms (synthetic lethality). Drug-induced PARP inhibition potentiates the activity of anticancer drugs such as 5-fluorouracil in enhancing DNA damage, whose repair involves PARP-1 activity. The aim of this study was to evaluate the inhibitory effects of a novel PARPI, HYDAMTIQ, on growth in human tumor cell lines characterized by different features with regard to DNA damage response pathways (BRCA mutational status, microsatellite status, and ATM expression level) and degree of sensitivity/resistance to 5-fluorouracil. HYDAMTIQ showed a more potent inhibitory effect on cell growth in a BRCA2 mutant cell line (CAPAN-1) compared with wild-type cells (C2-6, C2-12, and C2-14 CAPAN-1 clones, and MCF-7). No statistically significant difference was observed after HYDAMTIQ exposure between cells having a different MS status or a different MRE11 mutational status. HYDAMTIQ induced greater antiproliferative effects in SW620 cells expressing a low level of ATM than in H630 cells expressing a high level of ATM. Finally, the combination of HYDAMTIQ and 5-fluorouracil exerted a synergistic effect on the inhibition of SW620 cell growth and an antagonistic effect on that of H630 cell growth. Our results show that the novel PARP inhibitor HYDAMTIQ potently inhibits the growth of human tumor cells with defective DNA damage response pathways and exerts synergistic cytotoxicity in combination with 5-fluorouracil. These data provide relevant examples of synthetic lethality and evidence for further development of this novel PARPI.

Key words: PARP inhibitors (PARPIs); HYDAMTIQ; 5-Fluorouracil (5-FU); Human tumor cell lines; DNA damage response

Address correspondence to Enrico Mini, Department of Experimental and Clinical Medicine, University of Florence, Viale Pieraccini, 6, 50139 Firenze, Italy. Tel: +39-055-2758368; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Stefania Nobili, Department of Health Sciences, University of Florence, Viale Pieraccini, 6, 50139 Firenze, Italy. Tel: +39-055-2758386; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it