MicroRNA-645, up-regulated in human adencarcinoma of gastric esophageal junction, inhibits apoptosis by targeting tumor suppressor IFIT2

BMC Cancer

Xiaoshan Feng¹  Ying Wang¹  Zhikun Ma¹  Ruina Yang¹  Shuo Liang¹  Mengxi Zhang¹  Shiyuan Song¹  Shuoguo Li¹  Gang Liu¹  Daiming Fan²  Shegan Gao¹ 

[1] Oncology Department of the First Affiliated Hospital of Henan, University of Science and Technology, No. 24 Jinghua Road, Luoyang, Henan, China

[2] State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, China

关键词: Apoptosis;    IFIT2;    microRNA-645;    Adencarcinoma of gastric esophageal junction;   

Others  :  1121203
DOI  :  10.1186/1471-2407-14-633

 received in 2013-11-26, accepted in 2014-08-21,  发布年份 2014

【 摘 要 】

Background

An increasing body of evidence indicates that miRNAs have a critical role in carcinogenesis and cancer progression; however, the role of miRNAs in the tumorigenesis of adencarcinoma of gastric esophageal junction (AGEJ) remains largely unclear.

Methods

The SGC7901 and BGC-823 gastric cancer cell lines were used. The expressions of miR-645 and IFIT2 (Interferon-induced protein with tetratricopeptide repeats 2) were examined by qRT-PCR, The expressions of IFIT2 was examined by western blotting and immunohistochemistry assay. The cell apoptosis was determined by FACS. MiR-645 inhibitor, mimics and plasmid-IFIT2 transfections were performed to study the loss- and gain-function. Caspase-3/7 activity was examined by caspase-3/7 assay.

Results

In the present study, we have reported an increased expression of miR-645 in AGEJ clinical specimens compared with paired non-cancerous tissues. We also observed a significant miR-645 up-regulation in two gastric cancer (GC) cell lines, SGC7901 and BGC-823, which were used as cell models because there was no available AGEJ cell lines established to date. We found that inhibition of miR-645 could sensitize dramatically SGC7901 and BGC-823 cells to both serum starvation– and chemotherapeutic drug–induced apoptosis by up-regulating IFIT2, a mediator of apoptosis via a mitochondrial pathway, with a potential binding site for miR-645 in its mRNA’s 3′UTR. Further investigation exhibited that IFIT2 expression decreases in SGC7901 and BGC-823 cells and AGEJ tissues. IFIT2 ectopic expression leads to promotion of cell apoptosis, indicating that IFIT2 may function as a suppressor in the development of AGEJ. Furthermore, inhibition of miR-645 induces up-regulation of IFIT2 and increased caspase-3/7 activity compared with control groups.

Conclusions

Our data suggest that miR-645 functions as an oncogene in human AGEJ by, at least partially through, targeting IFIT2.

【 授权许可】

   
2014 Feng et al.; licensee BioMed Central Ltd.

【 图 表 】

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