Oncology Research 26(9) Abstracts

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Oncology Research, Vol. 26, pp. 1307-1315, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14928634401187
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Corilagin
Induces High Levels of Apoptosis in the Temozolomide-Resistant T98G Glioma Cell Line

Roberta Milani,* Eleonora Brognara,* Enrica Fabbri,* Alessia Finotti,* Monica Borgatti,* Ilaria Lampronti,* Giovanni Marzaro,† Adriana Chilin,† Kenneth Ka-Ho Lee,‡ Stanton Hon-Lung Kok,‡ Chung-Hin Chui,§ and Roberto Gambari*

*Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy
†Department of Pharmaceutical and Pharmacological Sciences, University of PadovaPadova, Italy
‡School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, P.R. China
§Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, P.R. China

Glioblastoma multiforme (GBM), a malignant tumor of the central nervous system, has a high mortality rate. No curative treatment is presently available, and the most commonly used chemotherapeutic drug, the alkylating agent temozolomide (TMZ), is only able to increase life expectancy and is often associated with drug resistance. Therefore, an urgent need does exist for novel drugs aimed at treating gliomas. In the present study, we obtained three major results using corilagin: (a) demonstrated that it inhibits the growth of U251 glioma cells through activation of the apoptotic pathway; (b) demonstrated that it is also active on TMZ-resistant T98G glioma cells; and (c) demonstrated that when used in combination with TMZ on T98G glioma cells, a higher level of proapototic and antiproliferative effects is observed. Our study indicates that corilagin should be investigated in more detail to determine whether it can be developed as a potential therapeutic agent. In addition, our results suggest that corilagin could be used in combination with low doses of other standard anticancer chemotherapeutic drugs against gliomas (such as TMZ) with the aim of obtaining enhanced anticancer effects.

Key words: Glioma; Temozolomide (TMZ); Corilagin (CORL); Apoptosis

Address correspondence to Professor Roberto Gambari, Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara n.74, 44121 Ferrara, Italy. Tel: +39-532-974443; Fax: +39-532-974500; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1317-1326, 2018
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DOI: https://doi.org/10.3727/096504018X
15179680859017
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Tumor-Suppressive MicroRNA-708 Targets Notch1 to Suppress Cell Proliferation and Invasion in Gastric Cancer

Xuyan Li,*1 Xuanfang Zhong,†1 Xiuhua Pan,‡ and Yan Ji§

*Clinical Laboratory Central, Huizhou Central People’s Hospital, Guangdong, P.R. China
†Department of Digestion, Huizhou Central People’s Hospital, Guangdong, P.R. China
‡Department of Radiotherapy, Huizhou Central People’s Hospital, Guangdong, P.R. China
§Department of Prenatal Diagnosis, Huizhou Central People’s Hospital, Guangdong, P.R. China

Growing evidence has demonstrated that numerous microRNAs (miRNAs) may participate in the regulation of gastric carcinogenesis and progression. This phenomenon suggests that gastric cancer-related miRNAs can be identified as effective therapeutic targets for this disease. miRNA-708 (miR-708) has recently been reported to be aberrantly expressed in several types of cancer and contribute to carcinogenesis and progression. However, the expression level, biological roles, and underlying mechanisms of miR-708 in gastric cancer are poorly understood. Here we found that miR-708 was downregulated in gastric cancer tissues and cell lines. Downregulated miR-708 expression was significantly associated with lymphatic metastasis, invasive depth, and TNM stage. Further investigation indicated that ectopic expression of miR-708 prohibited cell proliferation and invasion in gastric cancer. Bioinformatics analysis showed that Notch1 was a potential target of miR-708. Notch1 was further confirmed as a direct target gene of miR-708 in gastric cancer by dual-luciferase reporter assay, reverse transcription quantitative polymerase chain reaction, and Western blot analysis. Furthermore, an inverse association was found between miR-708 and Notch1 mRNA levels in gastric cancer tissues. In addition, restored Notch1 expression rescued the inhibitory effects on gastric cancer cell proliferation and invasion induced by miR-708 overexpression. Our findings highlight the tumor-suppressive roles of miR-708 in gastric cancer and suggest that miR-708 may be investigated as a novel target for gastric cancer treatment.

Key words: MicroRNA-708; Gastric cancer; Notch1; Proliferation; Invasion

1These authors provided equal contribution to this work.
Address correspondence to Xuyan Li, Clinical Laboratory Central, Huizhou Central People’s Hospital, No. 41 E’ling North Road, Huizhou, Guangdong 516001, 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. 1327-1334, 2018
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DOI: https://doi.org/10.3727/096504018X
15165493852990
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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MicroRNA-18a Targets IRF2 and CBX7 to Promote Cell Proliferation in Hepatocellular Carcinoma

Zhang Yongyu,* Yang Lewei,† Liu Jian,‡ and Sun Yuqin§

*Department of Interventional Radiology, the Fifth Affiliated Hospital of Sun Yat-sen University, Xiangzhou District, Zhuhai, P.R. China
†Department of Radiation Oncology, the Fifth Affiliated Hospital of Sun Yat-sen University, Xiangzhou District, Zhuhai, P.R. China
‡Department of Infectious Diseases, the Fifth Affiliated Hospital of Sun Yat-sen University, Xiangzhou District, Zhuhai, P.R. China
§Department of Nursing, the Fifth Affiliated Hospital of Sun Yat-sen University, Xiangzhou District, Zhuhai, P.R. China

MicroRNAs (miRNAs) are a family of noncoding RNAs of ~22 nt in length that play important roles in the tumor initiation and progression processes. The aberrant expression status of miR-18a has been reported in hepatocellular carcinoma (HCC). However, the biological role and the underlying mechanism of miR-18a in HCC progression are still to be elucidated. In this study, we examined the expression level of miR-18a in HCC cell lines using the quantitative real-time PCR method. We showed that miR-18a expression in human HCC cell lines was elevated compared with the normal liver cell line. Meanwhile, increasing miR-18a expression by an miR-18a mimic in HCC cell lines promoted cell proliferation and migration, while inhibiting miR-18a expression by an miR-18a inhibitor caused the opposite effects. Using the bioinformatic analyses method, we found that the 3′-untranslated regions (3′-UTRs) of interferon regulatory factor 2 (IRF2) and chromobox protein homolog 7 (CBX7) contain putative binding sequences for miR-18a. Further, luciferase assay validated that both IRF2 and CBX7 were the direct targets of miR-18a in HCC. Moreover, we revealed that overexpression of IRF2 and CBX7 has similar effects as miR-18a downregulation on HCC cell lines. Our results illustrated that miR-18a plays a positive role in HCC progression process by stimulating cell proliferation and migration partly through regulating IRF2 and CBX7.

Key words: miR-18a; Hepatocellular carcinoma (HCC); Interferon regulatory factor 2 (IRF2); Chromobox protein homolog 7 (CBX7); Proliferation; Migration

Address correspondence to Yang Lewei, Department of Radiation Oncology, the Fifth Affiliated Hospital of Sun Yat-sen University, No. 52 Meihua Dong Road, Xiangzhou District, Zhuhai 519000, 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. 1335-1343, 2018
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DOI: https://doi.org/10.3727/096504018X
15188367859402
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Long Noncoding RNA FEZF1-AS1 Promotes Osteosarcoma Progression by Regulating the miR-4443/NUPR1 Axis

Chengwei Zhou,1 Jianxiang Xu,1 Jinti Lin, Renjin Lin, Kai Chen, Jianzhong Kong, and Xiaolong Shui

Department of Orthopedics Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, P.R. China

Long noncoding RNA (lncRNA) FEZF1-AS1 was demonstrated to facilitate cell proliferation and migration in some cancers. However, the functions of FEZF1-AS1 and its molecular mechanism in osteosarcoma remain to be elucidated. In our study, we found that the expression of FEZF1-AS1 was upregulated in osteosarcoma samples and cell lines compared with normal tissues or cells. Besides, we showed that the expression levels of FEZF1-AS1 in osteosarcoma patients were positively correlated with tumor metastasis and TNM stage. Additionally, FEZF1-AS1 knockdown inhibited cell proliferation, migration, and invasion in U2OS and MG63 cells, while upregulation had the opposite effects in vitro. Moreover, FEZF1-AS1 depletion inhibited tumor growth and metastasis in vivo. We found that FEZF1-AS1 sponged miR-4443 to promote NUPR1 expression in U2OS and MG63 cells. Furthermore, knockdown of miR-4443 abrogated FEZF1-AS1 silencing-induced inhibition of cell proliferation, migration, and invasion in osteosarcoma. Finally, we found that restoration of NUPR1 rescued the proliferation, migration, and invasion abilities of FEZF1-AS1-depleted U2OS and MG63 cells. Our study indicated that FEZF1-AS1 could promote osteosarcoma progression by sponging miR-4443 to promote NUPR1 expression. The FEZF1-AS1/miR-4443/NUPR1 axis may act as a novel therapeutic strategy for osteosarcoma treatment.

Key words: FEZF1-AS1; miR-4443; NUPR1; Progression; Osteosarcoma

1These authors provided equal contribution to this work and are co-first authors.
Address correspondence to Xiaolong Shui, Department of Orthopedics Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, No. 109 Xue Yuan West Road, Wenzhou, Zhejiang Province 325027, 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. 1345-1353, 2018
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DOI: https://doi.org/10.3727/096504018X
15180508535835
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

miR-126 Functions as a Tumor Suppressor by Targeting SRPK1 in Human Gastric Cancer

Qiaorong Li,* Geng Wang,† and Hong Wang‡

*Department of Intensive Care Unit, Shandong Provincial Third Hospital, Jinan, Shandong, P.R. China
†Department of Emergency, Laiwu City People’s Hospital, Laiwu, Shandong, P.R. China
‡Department of General Surgery, Shandong Provincial Third Hospital, Jinan, Shandong, P.R. China

The expression of miR-126 and serine–arginine protein kinase 1 (SRPK1) are linked to tumor development; nevertheless, its role in the tumor growth and invasion of gastric cancer (GC) and the underlying mechanism have not been clarified. Here the expression and role of miR-126 and SRPK1 were investigated in GC tissues and cells by in vitro assay, and then targets of miR-126 were identified by dual-luciferase reporter assay. In this study, miR-126 expression was downregulated and associated with lymph node metastasis and poor prognosis as well as SRPK1 expression. In vitro assay revealed that miR-126 obviously inhibited the proliferative and invasive capabilities of GC cells. The dual-luciferase reporter assay showed that miR-126 targets the 3
¢-UTR of SRPK1 and downregulates its expression. SRPK1 overexpression promoted cell migration and invasion. In conclusion, the reduced expression of miR-126 is suggestive of the risk of GC recurrence and metastasis, and miR-126 functions as a tumor suppressor by targeting SRPK1 expression in the development of GC.

Key words: miR-126; SRPK1; Gastric cancer (GC)

Address correspondence to Hong Wang, Department of General Surgery, Shandong Provincial Third Hospital, No. 12, Central Wuying Hill Road, Jinan 250031, Shandong, 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. 1355-1363, 2018
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DOI: https://doi.org/10.3727/096504018X
15154094331876
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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MicroRNA-511 Inhibits Cellular Proliferation and Invasion in Colorectal Cancer by Directly Targeting Hepatoma-Derived Growth Factor

Saifei He,*1 Guangdong Wang,†1 Jing Ni,* Juhua Zhuang,* Suiliang Zhuang,‡ Guoyu Wang,* Ying Ye,* and Wei Xia*

*Department of Nuclear Medicine, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China
†Department of Research and Development, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China
‡Department of Oncology, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China

Dysregulated microRNA (miRNA) expression is involved in the occurrence and development of colorectal cancer (CRC) through the regulation of various important physiological events. Hence, miRNAs may be used as effective targets for CRC treatment; however, this hypothesis warrants further investigation. miRNA-511 (miR-511) plays vital roles in the progression of different tumor types. However, the expression, exact role, and the mechanisms underlying the regulation of colorectal carcinogenesis and progression by miR-511 remain poorly understood. This study presents that miR-511 expression was decreased in CRC tissues and cell lines compared with that in adjacent nonneoplastic tissues and normal human colon epithelium cell lines, respectively. The enforced expression of miR-511 in CRC cells significantly reduced cell proliferation and invasion. Hepatoma-derived growth factor (HDGF) was mechanically validated as a direct target of miR-511 in CRC. Furthermore, miR-511 was negatively associated with HDGF in CRC tissues. The restored HDGF expression can abrogate the tumor-suppressive roles of miR-511 in CRC cells. More importantly, miR-511 overexpression suppressed the PI3K/AKT signaling pathway in CRC. These results suggest that miR-511 can potentially serve as a therapeutic target for the therapy of patients with CRC.

Key words: Colorectal cancer (CRC); MicroRNA-511; Hepatoma-derived growth factor; Proliferation; Invasion

1These authors provided equal contribution to this work.
Address correspondence to Xia Wei, Department of Nuclear Medicine, The Seventh People’s Hospital of Shanghai University of TCM, 358 Datong Road, Pudong 200137, Shanghai, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Ying Ye, Department of Nuclear Medicine, The Seventh People’s Hospital of Shanghai University of TCM, 358 Datong Road, Pudong 200137, Shanghai, 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. 1365-1373, 2018
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DOI: https://doi.org/10.3727/096504018X
15154085345907
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Silencing of E3 Ubiquitin Ligase RNF8 Enhances Ionizing Radiation Sensitivity of Medulloblastoma Cells by Promoting the Deubiquitination of PCNA

Fei Li,*1 Bin Liu,†1 Xiaolan Zhou,* and Quan Xu‡

*College of Nursing, Xi’an Medical University, Xi’an, Shaanxi, P.R. China
†Department of Plastic Surgery, Xi’an Central Hospital, Xi’an, Shaanxi, P.R. China
‡Department of Pediatric Surgery, Northwest Women and Children’s Hospital, Xi’an, Shaanxi, P.R. China

DNA damage response induced by ionizing radiation (IR) is an important event involved in the sensitivity and efficiency of radiotherapy in human medulloblastoma. RNF8 is an E3 ubiquitin ligase and has key roles in the process of DNA damage and repair. Our study aimed to evaluate the effect of RNF8 in the DNA damage repair induced by IR exposure in medulloblastoma cells. We found that the levels of RNF8 were significantly upregulated by g-ray irradiation in a dose-dependent manner in medulloblastoma cells and colocalized with g-H2AX, a sensitive marker of DNA double-strand breaks induced by g-ray radiation. RNF8 knockdown was observed to enhance the sensitivity of IR in medulloblastoma cells, as evaluated by reduced cell survival. The apoptosis and cell cycle arrest of medulloblastoma cells were dramatically increased by RNF8 suppression after IR treatment. Furthermore, RNF8 inhibition did not affect the protein levels of BRCA1, a crucial protein involved in IR-induced DNA damage repair, but significantly decreased the recruitment of BRCA1 and increased the level of g-H2AX at DNA damage sites compared to the control. A significant increase in OTM was observed in medulloblastoma cells treated by RNF8 shRNA after exposure to IR, indicating the effect of RNF8 on DNA damage and repair. Additionally, PCNA, a major target for ubiquitin modification during DNA damage response, was found to be monoubiquitinated by E3 ligase RNF8 and might contribute to the low radiosensitivity in medulloblastoma cells. Altogether, our findings may provide RNF8 as a novel target for the improvement of radiotherapy in medulloblastoma.

Key words: RNF8; Ionizing radiation (IR); Sensitivity; PCNA ubiquitination; DNA damage; Medulloblastoma

1These authors provided equal contribution to this work.
Address correspondence to Xiaolan Zhou, College of Nursing, Xi’an Medical University, 1 Xinwang Road, Xi’an, Shaanxi, 710021, P.R. China. Tel: +86-2986168967; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1375-1382, 2018
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DOI: https://doi.org/10.3727/096504018X
15188352857437
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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miR-365 Suppresses Cholangiocarcinoma Cell Proliferation and Induces Apoptosis by Targeting E2F2

Lunjian Chen,* Xiaorong Huang,† and Xinxin Chen‡

*Department of Hepatobiliary Surgery, The Xinjiang Uygur Autonomous Region People’s Hospital, Urumqi, P.R. China
†Otorhinolaryngology Center, The Xinjiang Uygur Autonomous Region People’s Hospital, Urumqi, P.R. China
‡Department of Preventive Health Care, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, P.R. China

Cholangiocarcinoma (CCA) is one of the most malignant adenocarcinomas arising from bile duct epithelial cells. However, the molecular mechanism regulating CCA development and progression still needs to be investigated. Here we found that miR-365 was downregulated in CCA tissues compared with adjacent normal tissues. By functional experiments, we found that overexpression of miR-365 significantly inhibited CCA cell proliferation and promoted cellular apoptosis in vitro. Furthermore, administration with miR-365 markedly suppressed the growth of tumor tissues in vivo. Mechanistically, we identified E2F2 as the target gene of miR-365 in CCA cells. We found that overexpression significantly inhibited the expression of E2F2 in CCA cells, and there was an inverse correlation between the expression levels of E2F2 and miR-365 in CCA tissues. We also found that E2F2 was highly expressed in CCA tissues and cell lines. Restoration of E2F2 in miR-365-overexpressing CCA cells promoted cell viability and reduced cellular apoptosis in CCA. Collectively, our study demonstrated the essential role of miR-365 and its functional mechanism in CCA cells, which provided a new insight on the design of therapeutic targets for CCA treatment.

Key words: Cholangiocarcinoma (CCA); miR-365; Proliferation; Apoptosis; E2F transcription factor 2 (E2F2)

Address correspondence to Professor Lunjian Chen, Department of Hepatobiliary Surgery, The Xinjiang Uygur Autonomous Region People’s Hospital, No. 91 Tianchi Road, Urumqi, Xinjiang 830001, 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. 1383-1390, 2018
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DOI: https://doi.org/10.3727/096504018X
15188340975709
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Long Noncoding RNA CCAL Promotes Papillary Thyroid Cancer Progression by Activation of NOTCH1 Pathway

Ying Ye, Yanan Song, Juhua Zhuang, Saifei He, Jing Ni, and Wei Xia

Department of Nuclear Medicine, the Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China

Long noncoding RNA CCAL has been reported to promote tumor progression in various human cancers, including hepatocellular carcinoma, osteosarcoma, and colorectal cancer. However, the role of CCAL in papillary thyroid cancer remains largely unknown. In the present study, we found that the expression of CCAL was upregulated in papillary thyroid tumor tissues compared to adjacent normal tissues. Moreover, the expression of CCAL was positively related with papillary thyroid cancer severity and TNM stage and predicated poor prognosis. Besides, we found that knockdown of CCAL significantly inhibited papillary thyroid cancer cell proliferation, migration, and invasion in vitro and reduced tumor growth and metastasis in vivo. We found that knockdown of CCAL dramatically decreased the expression of NOTCH1 and suppressed the activation of the NOTCH1 signaling pathway. Furthermore, overexpression of NOTCH1 rescued the proliferation, migration, and invasion in papillary thyroid cancer cells. Taken together, our data indicated that CCAL promoted papillary thyroid cancer development and progression by activation of the NOTCH1 pathway, which provided a new insight on the design of therapeutic targets.

Key words: Papillary thyroid cancer; Colorectal cancer-associated lncRNA (CCAL); Proliferation; Migration; NOTCH1

Address correspondence to Professor Wei Xia, Department of Nuclear Medicine, the Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, No. 1200 Cai Lun Road, Shanghai 201203, 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. 1391-1399, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15178798885361
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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MicroRNA-139-3p Suppresses Tumor Growth and Metastasis in Hepatocellular Carcinoma by Repressing ANXA2R

Zeng Cheng Zou,*1 Min Dai,*1 Zeng Yin Huang,† Yi Lu,‡ He Ping Xie,* Yi Fang Li,§ Yue Li,* Ying Tan,¶ and Feng Lin Wang*

*Department of Integrated Traditional and Western Medicine, The Third Affiliated Hospital of SunYat-sen University, Guangzhou, P.R. China
†Department of Oncology Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, P.R. China
‡Department of Hepatobiliary Surgery, The Third Affiliated Hospital of SunYat-sen University, Guangzhou, P.R. China
§Department of Acupuncture, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, P.R. China
¶Department of Infertility and Sterility, Guangdong Provincial Family Planning Research Institute, Guangzhou, P.R. China

The direct roles of miR-139-3p on hepatocellular carcinoma (HCC) cell growth and metastasis remain poorly understood. We attempted to demonstrate the regulatory role of miR-139-3p in HCC progression and its underlying mechanisms. Here we showed that miR-139-3p expression was significantly reduced in the HCC tissues compared to paratumor tissues. Exogenous overexpression of miR-139-3p inhibited the migration and invasion of HCC cells, whereas downregulation of miR-139-3p was able to induce HCC HepG2 and SNU-449 cell migration and invasion. In addition, miR-139-3p inhibited HCC growth and lung metastasis in an in vivo mouse model, which is mainly regulated by annexin A2 receptor (ANXA2R). Finally, we identified that the expression of miR-139-3p was inversely correlated with ANXA2R expression in human HCC tissue. All these results demonstrated that miR-139-3p inhibited the metastasis process in HCC by downregulating ANXA2R expression.

Key words: MicroRNA 139-3p (miR-139-3p); Hepatocellular carcinoma (HCC); Annexin A2 receptor (ANXA2R); Metastasis

1These authors provided equal contribution to this work and are co-first authors.
Address correspondence to Dr. Feng Lin Wang, Department of Integrated Traditional and Western Medicine, The Third Affiliated Hospital of SunYat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou 510630, 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. 1401-1409, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15188747585738
E-ISSN 1555-3906
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MicroRNA-744 Inhibits Cellular Proliferation and Invasion of Colorectal Cancer by Directly Targeting Oncogene Notch1

Jian Shen and Minzhe Li

Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P.R. China

Accumulated studies have strongly implicated aberrantly expressed microRNAs (miRNAs) in carcinogenesis and cancer progression of various cancers, including colorectal cancer (CRC). Hence, a comprehensive study of miRNAs and their association with CRC may be a promising therapeutic method for patients with this malignancy. MicroRNA-744 (miR-744) is abnormally expressed in several types of human cancer. Thus far, little is known about the expression, biological roles, and exact mechanisms of miR-744 in CRC. Thus, the present study measured the expression level of miR-744 and investigated its roles and associated molecular mechanisms in CRC. This study demonstrated that miR-744 expression was significantly underexpressed in CRC tissues and cell lines. Low miR-744 expression was positively associated with lymphatic metastasis and TNM stage. Functional experiments revealed that miR-744 overexpression obviously inhibited the proliferation and invasion of CRC cells. Furthermore, Notch1 was identified as a direct target of miR-744 in CRC. Moreover, the inhibition of Notch1 phenocopied the inhibitory effects of miR-744 overexpression on CRC cells. Restored Notch1 expression markedly rescued the tumor-suppressive effects of miR-744 overexpression on CRC cells. Overall, miR-744 exhibits an essential role in CRC progression, and the miR-744/Notch1 axis may provide novel insights into future treatments for patients with CRC.

Key words: Colorectal cancer (CRC); MicroRNA-744 (miR-744); Notch1; Proliferation; Invasion

Address correspondence to Jian Shen, Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongtinan Road, Chaoyang District, Beijing 100020, 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. 1411-1418, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15190844870055
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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lncRNA
NORAD Contributes to Colorectal Cancer Progression by Inhibition of miR-202-5p

Jie Zhang*, Xiao-Yan Li*, Ping Hu†, and Yuan-Sheng Ding*

*The First Department of General Surgery, Linyi Central Hospital, Linyi, Shandong Province, P.R. China
†The First Department of Endocrinology, Linyi Central Hospital, Linyi, Shandong Province, P.R. China

Previous study indicates that long noncoding RNA NORAD could serve as a competing endogenous RNA to pancreatic cancer metastasis. However, its role in colorectal cancer (CRC) needs to be investigated. In the present study, we found that the expression of NORAD was significantly upregulated in CRC tissues. Furthermore, the expression of NORAD was positively related with CRC metastasis and patients’ poor prognosis. Knockdown of NORAD markedly inhibited CRC cell proliferation, migration, and invasion but induced cell apoptosis in vitro. In vivo experiments also indicated an inhibitory effect of NORAD on tumor growth. Mechanistically, we found that NORAD served as a competing endogenous RNA for miR-202-5p. We found that there was an inverse relationship between the expression of NORAD and miR-202-5p in CRC tissues. Moreover, overexpression of miR-202-5p in SW480 and HCT116 cells significantly inhibited cellular proliferation, migration, and invasion. Taken together, our study demonstrated that the NORAD/miR-202-5p axis plays a pivotal function on CRC progression.

Key words: NORAD; Colorectal cancer (CRC); Proliferation; Metastasis; miR-202-5p

Address correspondence to Yuan-Sheng Ding, The First Department of General Surgery, Linyi Central Hospital, No. 17 Yishui County, Linyi 276400, Shandong 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. 1419-1428, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15178768577951
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Long Noncoding RNA H19 Promotes Proliferation and Invasion in Human Glioma Cells by Downregulating miR-152

Lei Chen, Yuhai Wang, Jianqing He, Chunlei Zhang, Junhui Chen, and Dongliang Shi

Department of Neurosurgery, 101st Hospital of PLA (Wuxi Taihu Hospital), Clinical Medical School of Anhui Medical University, Wuxi, P.R. China

miR-152 and lncRNA H19 have been frequently implicated in various cellular processes including cell proliferation, invasion, angiogenesis, and apoptosis. However, the interaction between miR-152 and H19 in glioma has never been reported. RT-qPCR was used to examine the expression of miR-152 and H19 in human glioma cell lines and normal human astrocytes (NHAs). The interaction between miR-152 and lncRNA H19 was assessed by dual-luciferase reporter assay. MTT assay and Transwell invasion assay were used to determine the proliferation and invasion of U251 and U87 cells. A xenograft tumor experiment was performed to confirm the role of H19 in vivo. The results showed that H19 expression was upregulated and miR-152 expression was downregulated in human glioma cell lines. H19 downregulation or miR-152 upregulation suppressed glioma cell proliferation and invasion in vitro. Moreover, H19 and miR-152 directly regulated each other. Furthermore, decreased miR-152 expression alleviated si-H19-induced inhibitory effects on proliferation and invasion in glioma cells. As expected, H19 silencing hindered glioma growth in vivo. Taken together, H19 promoted glioma cell proliferation and invasion by negatively regulating miR-152 expression, providing evidence for the potential application of H19 as a biomarker and therapy target for glioma.

Key words: H19; Glioma; Long noncoding RNAs (lncRNAs); MicroRNAs (miRNAs); Proliferation; Invasion

Address correspondence to Yuhai Wang, Department of Neurosurgery, l01st Hospital of PLA (Wuxi Taihu Hospital), Clinical Medical School of Anhui Medical University, No. 101 XingYuan North Road, Wuxi, 214044, P.R. China. Tel: +86-55185142442; Fax: +86-55185142309; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1429-1437, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15186047251584
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA-331 Inhibits Proliferation and Invasion of Melanoma Cells by Targeting Astrocyte-Elevated Gene-1

Li Chen, Guozhang Ma, Xiaohui Cao, Xiaoxia An, and Xiguang Liu

Department of Dermatology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, P.R. China

Melanoma is characterized by aggressive invasion, early metastasis, and resistance to existing chemotherapeutic agents. Accumulated studies have reported that microRNA (miRNA) is a potentially robust molecular tool for developing future therapeutic technologies. Therefore, examining the expression patterns, biological roles, and associated mechanisms of cancer-related miRNAs in melanoma is essential for developing novel therapeutic targets for patients with this disease. In this study, miRNA-331 (miR-331) was underexpressed in melanoma tissues and cell lines. Functional assays revealed that the enforced expression of miR-331 inhibited cell proliferation and invasion. In addition, astrocyte-elevated gene-1 (AEG-1) was identified as a novel target of miR-331 through bioinformatics analysis, reverse transcription quantitative polymerase chain reaction analysis, Western blot analysis, dual-luciferase reporter assay, and Spearman’s correlation analysis. Furthermore, reintroduction of AEG-1 partially abrogated the inhibitory effects of miR-331 overexpression on the proliferation and invasion of melanoma cells. Moreover, miR-331 suppressed the activation of the PTEN/AKT signaling pathway in melanoma by inhibiting AEG-1. In short, miR-331 may play tumor-suppressive roles in melanoma by directly targeting AEG-1 and regulating the PTEN/AKT signaling pathway, suggesting that miR-331 could be investigated as a therapeutic strategy for patients with this malignancy.

Key words: MicroRNA-331 (miR-331); Melanoma; Astrocyte-elevated gene-1 (AEG-1); Proliferation; Invasion

Address correspondence to Xiguang Liu, Department of Dermatology, Heilongjiang Provincial Hospital, No. 82 Zhongshan Road, Harbin, Heilongjiang 150036, 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. 1439-1446, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15189093975640
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA-935 Inhibits Proliferation and Invasion of Osteosarcoma Cells by Directly Targeting High Mobility Group Box 1

Zhiqiang Liu,*1 Qiang Li,*1 Xin Zhao,† Bin Cui,* Libo Zhang,* and Qiang Wang*

*Department of Orthopedics, Daqing Long Nan Hospital, Daqing, Heilongjiang, P.R. China
†Department of Heart Noninvasive Examination, Daqing Oilfield General Hospital, Daqing, Heilongjiang, P.R. China

Numerous studies have suggested that microRNAs (miRNAs) are dysregulated in osteosarcoma (OS), implicating miRNAs in OS initiation and progression. Therefore, knowledge of aberrantly expressed miRNAs in OS may provide novel mechanistic insights into the tumorigenesis and tumor development of OS and facilitate therapeutic methods for patients with this aggressive bone neoplasm. In this study, data obtained from reverse transcription quantitative polymerase chain reaction (RT-qPCR) revealed that miR-935 was significantly decreased in OS tissues and cell lines. Restoration expression of miR-935 obviously restricted proliferation and invasion of OS cells. In addition, high-mobility group box 1 (HMGB1) was predicted to be a putative target of miR-935. Subsequent dual-luciferase reporter assay, RT-qPCR, and Western blot analysis confirmed that miR-935 could directly target the 3′-untranslated region of HMGB1 and negatively regulated HMGB1 expression in OS cells. Furthermore, a significant negative association was found between miR-935 and HMGB1 mRNA expression in OS tissues. Rescue experiments showed that recovery of HMGB1 expression partially rescued miR-935-induced suppression of cell proliferation and invasion in OS. These results provide the first evidence for the suppressive roles of miR-935 in OS by directly targeting HMGB1, suggesting that miR-935 may be a potential candidate for the treatment of patients with this disease.

Key words: MicroRNA-935; Osteosarcoma (OS); Proliferation; Invasion; High-mobility group box 1 (HMGB1)

1These authors provided equal contribution to this work.
Address correspondence to Qiang Li, Department of Orthopaedics, Da Qing Long Nan Hospital, No. 35 Aiguo Road, Daqing, Heilongjiang 163001, 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. 1447-1455, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15193823766141
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA-342 Prohibits Proliferation and Invasion of Melanoma Cells by Directly Targeting Zinc-Finger E-Box-Binding Homeobox 1

Quan Shi,*† Qi He,* and Jing Wei*

*Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, P.R. China
†Department of Dermatology, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, Hubei, P.R. China

As documented in numerous studies, microRNAs (miRNAs) play key roles in various biological processes associated with melanoma occurrence and development. In this study, we found that miRNA-342 (miR-342) was significantly downregulated in melanoma tissues and cell lines. Additionally, the ectopic expression of miR-342 prohibited the cell proliferation and invasion of melanoma. Moreover, zinc-finger E-box-binding homeobox 1 (ZEB1) was identified as a direct target gene of miR-342 in melanoma. Similar with the results induced by miR-342 overexpression, ZEB1 knockdown attenuated cell proliferation and invasion in melanoma. Furthermore, the restoration of ZEB1 expression reversed the suppressive effects of miR-342 on the proliferation and invasion of melanoma cells. These findings suggest that miR-342 may play tumor-suppressing roles in melanoma, at least partially, by directly inhibiting ZEB1 expression. Therefore, miR-342 may be developed as a potential candidate for the treatment of patients with this aggressive type of cancer.

Key words: Melanoma; MicroRNA-342 (miR342); Proliferation; Invasion; Zinc-finger E-box-binding homeobox 1 (ZEB1)

Address correspondence to Quan Shi, Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine. No. 4 Huayuanshan Road, Wuhan, Hubei 430061, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it