title: miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS.
abstract: Emerging evidence has shown the association of aberrantly expressed miR-106a with cancer development, however, little is known about its potential role in gastric carcinogenesis. In our present study, obviously overexpressed miR-106a was found in gastric cancer tissues compared with their nontumor counterparts. Suppression of miR-106a significantly inhibited gastric cancer cell proliferation and triggered apoptosis. Bioinformatic analysis combining with validation experiments identified FAS as a direct target of miR-106a. Rescue experiments and examination of caspase-8, PARP and caspase-3 further approved that miR-106a could inhibit gastric cancer cell apoptosis through interfering with FAS-mediated apoptotic pathway. Moreover, a significant inverse correlation was found between miR-106a and FAS expression not only in gastric cancer cell lines but also in gastric cancer specimens. Taken together, these findings suggest that ectopicly overexpressed miR-106a may play an oncogenic role in gastric carcinogenesis and impair extrinsic apoptotic pathway through targeting FAS.
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Zaozao
authors.initials: Z
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Shun
authors.initials: S
authors.lastname: He
authors.forename: Chenfei
authors.initials: C
authors.lastname: Hu
authors.forename: Lanping
authors.initials: L
authors.lastname: Quan
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Bai
authors.forename: Ningzhi
authors.initials: N
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D020029:Base Pairing; D001483:Base Sequence; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D016415:Sequence Alignment; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D019014:fas Receptor