Overexpression of miR-370 and downregulation of its novel target TGF[beta]-RII contribute to the progression of gastric carcinoma

• Published in: Oncogene Vol. 31; no. 2; p. 226
• Main Authors: Lo, S-s, Hung, P-s, Chen, J-h, Tu, H-f, Fang, W-l, Chen, C-y, Chen, W-t, Gong, N-r, Wu, C-w
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group 12.01.2012
• Subjects: Gastrointestinal diseases; Gene expression; Ribonucleic acid; RNA; Tumors
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2011.226

MicroRNAs (miRNAs) are endogenous non-coding RNAs that are known to be involved in the pathogenesis of tumors. Gastric carcinoma (GC) is a common malignancy worldwide. The aim of this study was the identification of the expression signature and functional roles of aberrant miRNAs in GC. Initial screening established a profile of aberrantly expressed miRNAs in tumors. miR-370 was confirmed to be overexpressed in GC tissues. Higher expression of miR-370 in GC tissues was associated with more advanced nodal metastasis and a higher clinical stage compared with controls. In addition, significantly higher level of miR-370 was noted in the plasma of GC patients compared with controls. Patients having more invasive or advanced tumors also exhibited a higher plasma level of miR-370. In vitro assays indicated that exogenous miR-370 expression enhanced the oncogenic potential of GC cells. The AGS-GFPM2 cells with exogenous miR-370 expression also exhibited enhanced abdominal metastatic dissemination in nude mice. Reporter assays confirmed that miR-370 targeted predicted sites in 3'UTR of transforming growth factor-β receptor II (TGFβ-RII) gene. The exogenous miR-370 expression decreased TGFβ-RII expression and the phosphorylation of Smad3 elicited by TGFβ1. The TGFβ1-mediated repression in cell migration was reverted by exogenous miR-370 expression. A reverse correlation between miR-370 and TGFβ-RII expression was noted in GC tissues. This study concludes that miR-370 is a miRNA that is associated with GC progression by downregulating TGFβ-RII. The miRNA expression profile described in this study should contribute to future studies on the role of miRNAs in GC.