title: MicroRNA-645, up-regulated in human adencarcinoma of gastric esophageal junction, inhibits apoptosis by targeting tumor suppressor IFIT2.
abstract: 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.
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Feng
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Ma
authors.forename: Ruina
authors.initials: R
authors.lastname: Yang
authors.forename: Shuo
authors.initials: S
authors.lastname: Liang
authors.forename: Mengxi
authors.initials: M
authors.lastname: Zhang
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Song
authors.forename: Shuoguo
authors.initials: S
authors.lastname: Li
authors.affiliation: Oncology Department of the First Affiliated Hospital of Henan, University of Science and Technology, No, 24 Jinghua Road, Luoyang, Henan, China. liugang72@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
authors.forename: Shegan
authors.initials: S
authors.lastname: Gao
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; C484289:IFIT2 protein, human; C000598122:MIRN645 microRNA, human; D035683:MicroRNAs; D011506:Proteins; D016601:RNA-Binding Proteins