Open AccessSMG‐1 inhibition by miR‐192/‐215 causes epithelial‐mesenchymal transition in gastric carcinogenesis via activation of Wnt signaling
Author(s) -
Zhang Xiaojing,
Peng Yin,
Huang Yong,
Yang Mengting,
Yan Ruibin,
Zhao Yanqiu,
Cheng Yulan,
Liu Xi,
Deng Shiqi,
Feng Xianling,
Lin Huijuan,
Yu Huimin,
Chen Si,
Zhao Zhenfu,
Li Shanni,
Li Kuan,
Wang Liang,
Wei Yanjie,
He Zhendan,
Fan Xinmin,
Meltzer Stephen J.,
Li Song,
Jin Zhe
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1237
Subject(s) - wnt signaling pathway , signal transduction , microrna , western blot , biology , microbiology and biotechnology , carcinogenesis , cancer research , chemistry , gene , biochemistry
SMG ‐1,a member of the phosphoinositide kinase‐like kinase family, functioned as a tumor suppressor gene. However, the role of SMG ‐1 in GC remain uncharacterized. In this study, regulation of SMG ‐1 by miR‐192 and‐215, along with the biological effects of this modulation, were studied in GC . We used gene microarrays to screening and luciferase reporter assays were to verify the potential targets of miR‐192 and‐215. Tissue microarrays analyses were applied to measure the levels of SMG ‐1 in GC tissues. Western blot assays were used to assess the signaling pathway of SMG ‐1 regulated by miR‐192 and‐215 in GC . SMG ‐1 was significantly downregulated in GC tissues.The proliferative and invasive properties of GC cells were decreased by inhibition of miR‐192 and‐215, whereas an SMG ‐1si RNA rescued the inhibitory effects. Finally, SMG ‐1 inhibition by miR‐192 and‐215 primed Wnt signaling and induced EMT . Wnt signaling pathway proteins were decreased markedly by inhibitors of miR‐192 and‐215, while SMG ‐1 si RNA reversed the inhibition apparently. Meanwhile, miR‐192 and‐215 inhitibtors increased E‐cadherin expression and decreased N‐cadherin and cotransfection of SMG ‐1 si RNA reversed these effects. In summary, these findings illustrate that SMG ‐1 is suppressed by miR‐192 and‐215 and functions as a tumor suppressor in GC by inactivating Wnt signaling and suppressing EMT .