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Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma

Oncogene volume 31, pages 226–237 (2012)Cite this article

Abstract

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.

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Acknowledgements

We acknowledge helps from Dr Shu-Chun Lin, Dr Kuo-Wei Chang, Ms Yu-Pin Chen, Mr Shi-Wen Chen and Mr Chung-Sheng Chou. This study was supported by grant 96-2314-B-010-055-MY3 from National Science Council, and National Yang-Ming University Hospital Grant RD 2008-001.

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Authors and Affiliations

  1. Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    S-S Lo, W-L Fang, C-Y Chen, W-T Chen & C-W Wu

  2. Department of Surgery, National Yang-Ming University Hospital, Yi-Lan, Taiwan

    S-S Lo, C-Y Chen & W-T Chen

  3. Department of Dentistry, National Yang-Ming University Hospital, Yi-Lan, Taiwan

    P-S Hung, H-F Tu & N-R Gong

  4. Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    J-H Chen, W-L Fang & C-W Wu

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  1. S-S Lo
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Correspondence to S-S Lo.

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Lo, SS., Hung, PS., Chen, JH. et al. Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma. Oncogene 31, 226–237 (2012). https://doi.org/10.1038/onc.2011.226

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