MicroRNA-1225-5p inhibits proliferation and metastasis of gastric carcinoma through repressing insulin receptor substrate-1 and activation of β-catenin signaling
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Haiyin Zheng1,2,*, Fuxing Zhang1,3,*, Xinjian Lin1,4, Changming Huang5, Yiqin Zhang1, Yun Li1, Jianyin Lin1, Wannan Chen1,2, Xu Lin1,2
1Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
2Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
3Department of General Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China
4Department of Medicine and UC San Diego Moores Cancer Center, University of California-San Diego, La Jolla, CA, USA
5Department of General Surgery, Union Hospital of Fujian Medical University, Fuzhou, China
*These authors have contributed equally to this work
Xu Lin, e-mail: email@example.com
Wannan Chen, e-mail: firstname.lastname@example.org
Keywords: microRNA, microRNA-1225-5p, gastric cancer, insulin receptor substrate-1, β-catenin
Received: September 02, 2015 Accepted: December 02, 2015 Published: December 14, 2015
Emerging evidence has linked aberrantly expressed microRNAs (miRNAs) with oncogenesis and malignant development in various human cancers. However, their specific roles and functions in gastric carcinoma (GC) remain largely undefined. In this study we identify and report a novel miRNA, miR-1225-5p, as tumor suppressor in GC development and progression. Microarray analysis revealed that there were fifty-six differentially expressed miRNAs (thirty-two upregulated and twenty-four downregulated) in GC tumor samples compared to their corresponding nontumorous tissues. Downregulation of miR-1225-5p was frequently detected in GC and strongly correlated with more aggressive phenotypes and poor prognosis. Functional assays demonstrated that ectopic overexpression of miR-1225-5p could inhibit cell proliferation, colony formation, migration and invasion in vitro, as well as suppress tumor growth and metastasis in nude mice. Further integrative and functional studies suggested insulin receptor substrate 1 (IRS1) as a downstream effector of miR-1225-5p which acted through β-catenin signaling pathway. These results demonstrate that miR-1225-5p serves to constrain GC growth and metastatic potential via inhibition of IRS1 and β-catenin signaling. Therefore, downregulation of miR-1225-5p is likely to be one of major molecular mechanisms accounting for the development and progression of GC.
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