| Title | SMG-1 inhibition by miR-192/-215 causes epithelial-mesenchymal transition in gastric carcinogenesis via activation of Wnt signaling |
| Authors | 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 |
| Affiliation | Shenzhen Univ, Sch Med, Dept Pathol, 3688 Nanhai Ave,Rm 703, Shenzhen 518060, Guangdong, Peoples R China. Shenzhen Univ, Sch Med, Guangdong Key Lab Genome Stabil & Dis Prevent, Shenzhen Key Lab Micromol Innovatal Drugs,Shenzhe, Shenzhen, Guangdong, Peoples R China. Wuhan Univ, Sch Basic Med Sci, Dept Pathol, Wuhan, Hubei, Peoples R China. Peking Univ, Lab Chem Genom, Shenzhen Grad Sch, Shenzhen, Guangdong, Peoples R China. Johns Hopkins Univ, GI Div, Dept Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Guangzhou Med Univ, Dept Pathol & Pathophysiol, Guangzhou, Guangdong, Peoples R China. Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen, Guangdong, Peoples R China. Guangdong Prov Key Lab Mol Oncol Pathol, Guangzhou, Guangdong, Peoples R China. Shenzhen Univ, Sch Med, Dept Pathol, 3688 Nanhai Ave,Rm 703, Shenzhen 518060, Guangdong, Peoples R China. Li, S (reprint author), Peking Univ, Lab Chem Genom, Shenzhen Grad Sch, Shenzhen, Guangdong, Peoples R China. |
| Keywords | EMT gastric cancer miR-192/-215 SMG-1 Wnt signaling pathway TUMOR PROGRESSION CELL CARCINOMA CANCER BETA METASTASIS SUPPRESSOR EXPRESSION PATHWAY PROTEIN KINASE |
| Issue Date | 2018 |
| Publisher | CANCER MEDICINE |
| Citation | CANCER MEDICINE. 2018, 7(1), 146-156. |
| Abstract | 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-1siRNA 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 siRNA reversed the inhibition apparently. Meanwhile, miR-192 and-215 inhitibtors increased E-cadherin expression and decreased N-cadherin and cotransfection of SMG-1 siRNA 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. |
| URI | http://hdl.handle.net/20.500.11897/502735 |
| ISSN | 2045-7634 |
| DOI | 10.1002/cam4.1237 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 深圳研究生院待认领 |
