Oncotarget

Research Papers:

Downregulated miR-31 level associates with poor prognosis of gastric cancer and its restoration suppresses tumor cell malignant phenotypes by inhibiting E2F2

Huaidong Wang, Xiaotian Zhang, Yuxin Liu, Zhaohui Ni, Yan Lin, Zipeng Duan, Yue Shi, Guoqing Wang and Fan Li _

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Oncotarget. 2016; 7:36577-36589. https://doi.org/10.18632/oncotarget.9288

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Abstract

Huaidong Wang1,*, Xiaotian Zhang1,*, Yuxin Liu1, Zhaohui Ni1, Yan Lin1, Zipeng Duan1, Yue Shi1, Guoqing Wang1,2, Fan Li1,2

1Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin, China

2The Key Laboratory for Bionics Engineering, Ministry of Education, Jilin University, Changchun, Jilin, China

*These authors contributed equally to this work

Correspondence to:

Guoqing Wang, email: [email protected]

Fan Li, email: [email protected]

Keywords: gastric cancer, miRNA, miR-31, E2F2, biomarker

Received: November 16, 2015     Accepted: April 22, 2016     Published: May 11, 2016

ABSTRACT

The miRNA microarray analysis showed that miR-31 was reduced in gastric cancer. This study further assessed miR-31 expression and role of miR-31 in gastric cancer tissues and cell lines. The data showed that miR-31 expression was down-regulated in 40 cases of gastric cancer tissues compared to the adjacent normal tissues, and low expression of miR-31 was associated with poor tumor differentiation, lymph node metastasis, advanced T stage and worse overall survival of gastric cancer patients. Ectopic expression of miR-31 reduced tumor cell viability, enhanced apoptosis, arrested tumor cells at G1 transition, and reduced tumor cell migration and invasion in SGC-7901 and MGC-803 gastric cell lines in vitro. Enforced expression of miR-31 also inhibited growth of engrafted tumors in vivo. Luciferase reporter assays and western blot revealed that E2F2 is the direct target of miR-31. E2F2 expression was upregulated in gastric cancer tissues, and inversely associated with miR-31 levels, while knockdown of E2F2 expression mimicked miR-31 anti-tumor activity in gastric cancer cells, but the ectopic expression of E2F2 rescued the miR-31-mediated inhibition in gastric cell lines. Taken together, these results demonstrated that miR-31 acts as a crucial tumor suppressive activity by inhibiting E2F2s expression. Thus, miR-31 might be a candidate therapeutic target for gastric cancer patients.


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