Oncology Research 23(6) Abstracts

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Oncology Research, Vol. 23, pp. 267-274, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14549667333963
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

RNAi-Mediated Downregulation of FKBP14 Suppresses the Growth of Human Ovarian Cancer Cells

Meng Lu,1 Yi Miao,1 Lan Qi, Mingzhu Bai, Jiarong Zhang, and Youji Feng

Department of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China

FKBP14 belongs to the family of FK506-binding proteins (FKBPs). Altered expression of FKBPs has been reported in several malignancies. This study aimed to reveal the expression profile of FKBP14 in ovarian cancer and evaluate whether FKBP14 is a molecular target for cancer therapy. We found that the FKBP14 mRNA level was significantly higher in ovarian cancer tissues than in normal tissues. FKBP14 expression was then knocked down in two ovarian cancer cell lines, SKOV3 and HO8910 cells, by a lentiviral short hairpin RNA (shRNA) delivery system. Reduced expression of FKBP14 markedly impaired the proliferative ability of ovarian cancer cells. Additionally, ovarian cancer cells infected with FKBP14 shRNA lentivirus tended to arrest in the G0/G1
phase and undergo apoptosis. Moreover, knockdown of FKBP14 induced cell apoptosis via increasing the ratio of Bax to Bcl-2. These results indicated that FKBP14 might be a diagnostic marker for ovarian cancer and could be a potential molecular target for the therapy of ovarian cancer.

Key words: FKBP14; Ovarian cancer; Cell proliferation; Cell cycle; Cell apoptosis

1These authors provided equal contribution to this work.
Address correspondence to Dr. Youji Feng, Department of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University, 100 Haining Road, Hongkou District, Shanghai, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 275-282, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14562725373798
E-ISSN 1555-3906
Copyright
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miR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer via Reduction of SOD2

YaJie Cui,*† Kai’e She,‡ Defu Tian,§ Peilian Zhang,† and Xiaoyan Xin*

*Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
†Department of Obstetrics and Gynecology, Xi’an No. 1 Hospital, Xi’an, China
‡Department of Obstetrics and Gynecology, Shaanxi Provincial People’s Hospital, Xi’an, China
§Department of General Surgery, Shaanxi Provincial Fourth People’s Hospital, Xi’an, China

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, accounting for 90% of all ovarian cancer. Dysregulation of miRNAs is associated with several types of EOC. In the current research, we aimed to study the role of abnormal expression of miR-146a in the development of EOC and to elucidate the possible molecular mechanisms. Compared with control samples, mRNA expression of miR-146a was significantly decreased in EOC tissues and cell lines. Overexpression of miR-146a prohibited cell proliferation, enhanced apoptosis, and increased sensitivity to chemotherapy drugs in EOC cells. In contrast, downregulation of miR-146a promoted cell proliferation, suppressed apoptosis, and decreased sensitivity to chemotherapy drugs in EOC cells. Overexpression of miR-146a increased the reactive oxygen species (ROS) level and decreased SOD2 mRNA and protein expression. Downregulation of miR-146a increased SOD2 mRNA and protein expression. Overexpression of SOD2 significantly inhibited miR-146a mimics-induced suppression of cell proliferation and the increase of apoptosis and chemosensitivity. In conclusion, we identify miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates the expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and enhanced sensitivity to chemotherapy. The data demonstrate that the miR-146a/SOD2/ROS pathway may serve as a novel therapeutic target and prognostic marker in patients with EOC.

Key words: miR-146a; SOD2; Epithelial ovarian cancer (EOC); Proliferation; Apoptosis; Chemosensitivity

Address correspondence to Xiaoyan Xin, Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi’an 710033, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 283-290, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14562725373833
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

MicroRNA-92a Promotes Colorectal Cancer Cell Growth and Migration by Inhibiting KLF4

Huiqing Lv,* Zhongmin Zhang,† Yaoxia Wang,† Chenglin Li,† Weihong Gong,† and Xin Wang†

*Department of Hyperbaric Oxygen, Linyi People’s Hospital, Linyi, China
†Department of Oncology, Linyi People’s Hospital, Linyi, China

Colorectal cancer (CRC) is the third most common malignancy with high mortality around the world. However, the biological mechanism of CRC carcinogenesis is not completely known. In the present study, we determined the role of miR-92a in the regulation of CRC cell motility. Expression of miR-92a is aberrantly upregulated in human CRC tissues and cultured cells, as shown by RT-PCR analysis. The effects of miR-92a on the proliferation and migration of human CRC SW620 and LoVo cells were measured by CCK-8 and Transwell assay, respectively. Results showed that the proliferation and migration capacity of both SW620 and LoVo cells were significantly increased by miR-92a mimic transfection but reduced by miR-92a inhibition. Additionally, KLF4 was identified as a direct target of miR-92a in CRC cells through bioinformatics and luciferase reporter analysis. KLF4 overexpression attenuated the effects of miR-92a on the regulation of CRC cell motility. Further studies suggested that the cell cycle inhibitor p21 was aberrantly downregulated in CRC cells, whereas this inhibition was reversed by miR-92a inhibitor. In conclusion, our data demonstrated that miR-92a may play a positive role in the colorectal carcinogenesis by promoting the proliferation and migration of CRC cells through targeting KLF4 as well as downstream p21. This could be an alternative therapeutic target for CRC.

Key words: miR-92a; Colorectal cancer (CRC); KLF4; p21; Proliferation; Migration

Address correspondence to Xin Wang, Department of Oncology, Linyi People’s Hospital, Jiefang Road East Section No. 27, Lanshan District, Shandong Province, Linyi 276003, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 291-302, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14562725373879
E-ISSN 1555-3906
Copyright
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Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: An Observational Study

Zhiying Shao,*† Shalini Chaudhri,‡ Meng Guo,§ Longzhen Zhang,¶ and Daniel Rea#

*School of Cancer Sciences, University of Birmingham, Birmingham, UK
†Department of Medical Oncology, Affiliated Hospital of Xuzhou Medical College, Jiangsu, China
‡Department of Histopathology, University Hospital Birmingham, Birmingham, UK
§Department of Breast and Thyroid Surgery, Affiliated Hospital of Xuzhou Medical College, Jiangsu, China
¶Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical College, Jiangsu, China
#Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, UK

Triple negative breast cancer (TNBC) is a phenotype of breast cancer with aggressive clinical behavior. Because of the absence of optimal treatment, the prognosis of this disease is poor. The main purpose of this study was to detect the response to neoadjuvant chemotherapy (NACT) in a TNBC cohort and compare the long-term survival between patients with and without pathological complete response (pCR). A total of 53 patients diagnosed with TNBC from 2005 to 2013 who received NACT at the University Hospital Birmingham were enrolled in this study. Overall survival (OS) and progression-free survival (PFS) were compared between the pCR group and non-pCR group. Demographic information and clinical or pathologic parameters were also analyzed to explore potential predictive and prognostic factors. Fourteen patients (26.4%) achieved pCR to NACT. In univariate analysis, patients with pCR had longer PFS time (
p = 0.013) and OS time (p = 0.054) compared with their counterparts without pCR. In multivariate analysis, the existence of lymphovascular invasion (LVI) significantly reduced OS (HR = 17.404, 95% CI = 2.923–103.644) and PFS (HR = 7.776, 95% CI = 1.645–36.753). The achievement of pCR to NACT can significantly postpone the incidence of disease progression in patients with TNBC. There is not enough evidence showing its influence on ultimate survival. LVI may be a more potent prognostic factor than pCR in the TNBC cohort.

Key words: Breast cancer; Triple negative; Neoadjuvant chemotherapy (NACT); Pathological complete response (pCR)

Address correspondence to Longzhen Zhang, Department of Radiation Oncology, the Affiliated Hospital of Xuzhou Medical College, No. 99 West Huaihai Road, Xuzhou, Jiangsu, 221000, China. Tel: +86-15895236960; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Daniel Rea, Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. Tel: +44 (0) 1214145345; Fax: +44 (0) 1214143700; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 303-309, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14567549091305
E-ISSN 1555-3906
Copyright
© 2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Knockdown of Long Noncoding RNA GHET1 Inhibits Cell Proliferation and Invasion of Colorectal Cancer

Jianyu Zhou,* Xiaorong Li,* Meirong Wu,† Changwei Lin,* Yihang Guo,* and Buning Tian*

*Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
†Operation Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

Emerging evidence has identified the vital role of long noncoding RNAs (lncRNAs) in the development of colorectal cancer. In this study, we aimed to investigate the role of lncRNA gastric carcinoma highly expressed transcript 1 (GHET1) in colorectal cancer. We analyzed the expression of GHET1 in colorectal cancer (CRC) tissues by using ISH. We found that GHET1 expression was significantly increased in the CRC samples compared with adjacent tissues. Furthermore, the cancer tissues had higher GHET1 mRNA levels than their matched adjacent tissues. GHET1 expression was also significantly increased in the CRC cell lines compared with human normal colon epithelial cells. Downregulation of GHET1 mediated by shRNA suppressed the proliferation, cell cycle arrest, migration, and invasion of colorectal cancer cells in vitro. In addition, inhibition of GHET1 reversed the epithelial–mesenchymal transition in colorectal cancer cell lines. Taken together, our results suggest the potential use of GHET1 as a therapeutic target of colorectal cancer.

Key words: Long noncoding RNAs (lncRNAs); Colorectal cancer (CRC); Gastric carcinoma highly expressed transcript 1 (GHET1); Invasion; Proliferation; Epithelial–mesenchymal transition (EMT)

Address correspondence to Buning Tian, Department of General Surgery, The Third Xiangya Hospital of Central South University, Tongzipo Road No. 138, Changsha, Hunan 410013, China. Tel: +86-0731-88953543; Fax: +86-0731-88953543; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 311-320, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14567549091341
E-ISSN 1555-3906
Copyright
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TTF1-NPs Induce ERS-Mediated Apoptosis and Inhibit Human Hepatoma Cell Growth In Vitro and In Vivo

Bin Xiao,*1 Chao Liu,*†1 Bing-tong Liu,*1 Xuan Zhang,* Rong-rong Liu,* and Xue-Wu Zhang*

*College of Medicine, Yanbian University, Yanji, Jilin Province, China
†Affiliated Hospital, Yanbian University, Yanji, Jilin Province, China

Previous studies have shown that 5,2
,4-trihydroxy-6,7,5-trimethoxyflavone (TTF1) is the primary anticancer constituent of the traditional Chinese medicinal plant Sorbaria sorbifolia (SS), which has been applied to treat cancer in China. In this study, we investigated the in vitro and in vivo antitumor effects and biological mechanisms of small-molecule TTF1 nanoparticles (TTF1-NPs). The effects of TTF1-NPs on cell growth and apoptosis were investigated using human hepatoma cells. The molecular changes associated with the effects of TTF1-NPs were analyzed by immunocytochemistry and Western blot analysis. The in vivo effect of TTF1-NPs was investigated using the HepG2 tumor xenograft model. We found that TTF1-NPs exhibited antitumor effects in vitro accompanied by induction of apoptosis in human hepatoma cells. Mechanistically, our data showed that TTF1-NPs induced apoptosis via endoplasmic reticulum stress (ERS) pathway in hepatoma cells. Moreover, inhibition of ERS activation blocked TTF1-NP-induced apoptosis in HepG2 cells. Finally, TTF1-NPs inhibited the growth of HepG2 xenograft tumors. Taken together, our results demonstrated that TTF1-NP-induced apoptosis was mediated at least in part by the ERS pathway and thus inhibited hepatoma tumor growth.

Key words: Sorbaria sorbifolia; Traditional chinese medicine; Hepatoma; TTF1; Endoplasmic reticulum stress; Apoptosis; HepG2; Nanoparticles

1These authors provided equal contribution to this work.
Address correspondence to Xue-Wu Zhang, Professor, College of Medicine, Yanbian University, Yanji 133002, Jilin Province, China. Tel: +86-433-2435102; Fax: +86-433-2435104; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 321-326, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14570992647041
E-ISSN 1555-3906
Copyright
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Printed in the USA. All rights reserved

Therapeutic Injection of a C-Type CpG ODN Induced an Antitumor Immune Response in C57/BL6 Mice of Orthotopically Transplanted Hepatocellular Carcinoma

Huijie Jia,*†1 Tiesuo Zhao,‡§1 Di Zou,¶ Xiaolong Jia,§ Ji Gao,# and Xiangfeng Song‡§

*Department of Pathology, Xinxiang Medical University, Xinxiang, Henan, China
†Laboratory of Transplantation and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China
‡Department of Immunology, Xinxiang Medical University, Xinxiang, Henan, China
§Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, China
¶Department of Nephrology, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin, China
#Department of Urinary Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China

Synthetic CpG oligodeoxynucleotides (ODNs), as TLR9 agonists, have been found to play a possible role in antitumor effect. In order to determine the effect of YW002, known as a C-type CpG ODN, on the treatment of hepatocellular carcinoma (HCC), which is one of the most aggressive carcinomas, we chose to inject YW002 at the doses of 12.5 μg and 25 μg per mouse 7 days post-tumor challenge. The survival rate of mice was recorded every day. On day 14 postinjection, five mice in each group were bled and randomly sacrificed. The level of IFN-
γ or TNF-α in the serum was detected and lymphocyte infiltration in the tumor tissue; the ratios of CD8+ T cells and CD4+ T cells in the spleen of mice were also analyzed. The results indicated that treatment with YW002 could raise the survival rate and delay tumor growth in the mice with orthotopically transplanted HCC. Furthermore, the treatment improved the antitumor immune response through increasing the T-cell infiltration in tumor and the ratio of CD4+, CD8+, and NK cells in the spleen. In addition, the concentration of IFN-γ was raised, and the level of TGF-β was depressed. Our data suggested that CpG ODN might be a proper medicament in a monotherapeutic regimen for treatment of HCC.

Key words: CpG oligodeoxynucleotides (ODNs); Hepatocellular carcinoma (HCC); Immune cells; Cytokines

1These authors provided equal contribution to this work.
Address correspondence to Xiangfeng Song, Department of Pathology, Xinxiang Medical University, Jinsui Street 601, Xinxiang, Henan 453000, China. Tel/Fax: +86-03733831939; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Ji Gao, Department of Urinary Surgery, China-Japan Union Hospital, Jilin University, Xiantai Street 126, Changchun, Jilin 130033, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it