Abstract
BackgroundAn 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.MethodsThe 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.ResultsIn 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.ConclusionsOur data suggest that miR-645 functions as an oncogene in human AGEJ by, at least partially through, targeting IFIT2.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-633) contains supplementary material, which is available to authorized users.
Highlights
An increasing body of evidence indicates that miRNAs have a critical role in carcinogenesis and cancer progression; the role of miRNAs in the tumorigenesis of adencarcinoma of gastric esophageal junction (AGEJ) remains largely unclear
Some miRNAs can act as oncogenes [24,25,26] or tumor supressors [27,28] by regulating the expression of their target genes which have important roles in some key pathways involved in cell cycle progression, apoptosis or proliferation. miRNAs down-regulated in tumour specimens such as miR-22 [29,30], miR-101 [31,32], and miR-7 [33,34] usually function as suppressive miRNAs, while miRNAs upregulated in tumour specimens such as miR-17 [35,36], and miR-21 [37,38] usually exert oncogenic roles
We investigated whether miR-645 is up-regulated in human adencarcinoma of gastric esophageal junction and inhibits apoptosis by targeting tumor suppressor IFIT2
Summary
An increasing body of evidence indicates that miRNAs have a critical role in carcinogenesis and cancer progression; the role of miRNAs in the tumorigenesis of adencarcinoma of gastric esophageal junction (AGEJ) remains largely unclear. Some miRNAs can act as oncogenes [24,25,26] or tumor supressors [27,28] by regulating the expression of their target genes which have important roles in some key pathways involved in cell cycle progression, apoptosis or proliferation. MiRNAs down-regulated in tumour specimens such as miR-22 [29,30], miR-101 [31,32], and miR-7 [33,34] usually function as suppressive miRNAs, while miRNAs upregulated in tumour specimens such as miR-17 [35,36], and miR-21 [37,38] usually exert oncogenic roles These studies suggest that dysregulation of miRNAs is frequently involved in carcinogenesis and cancer progression
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