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MicroRNA 520d-3p inhibits gastric cancer cell proliferation, migration, and invasion by downregulating EphA2 expression

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Abstract

Aberrant expression of microRNAs (miRNAs) has been shown to play important roles in cancer progression as a result of changes in expression of their target genes. In this study, we investigated the roles of miR-520d-3p on gastric cancer (GC) cell proliferation, migration, and invasion, and confirmed that this miRNA regulates EphA2 expression. The mRNA expression levels of miR-520d-3p and EphA2 in GC tissues and cell lines were evaluated. The clinical and prognostic significance of miR-520d-3p was assessed. The biological function of miR-520d-3p in GC cells was investigated using a methylthiazolyldiphenyl-tetrazolium bromide assay, cell cycle assay, transwell invasion assay, and wound-healing assay. miR-520d-3p expression was down-regulated and inversely correlated with the expression of EphA2 in GC tissues and cell lines. Lower expression of miR-520d-3p was associated with tumor invasion (P = 0.0357), lymph nodes metastasis (P = 0.0272), a higher clinical stage (P = 0.0041), and poorer overall survival (P = 0.0105). Luciferase assays revealed that miR-520d-3p inhibited EphA2 expression by targeting the 3′-untranslated region of EphA2 mRNA. Overexpression of miR-520d-3p dramatically inhibited the proliferation, cell cycle progression, invasion, and migration of GC cells, while down-regulation substantially promoted these properties. Moreover, c-Myc, CyclinD1, and matrix metalloproteinase-9 expression levels were down-regulated in miR-520d-3p mimic-transfected cells and up-regulated in miR-520d-3p inhibitor-transfected cells. Taken together, our data showed that miR-520d-3p appears to contribute to GC progression via the regulation of EphA2 and could serve as a novel prognostic and potential therapeutic marker.

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Acknowledgments

This study was supported by the National Natural Scientific Foundation of China (No. 81172297), and the Fundamental Research Funds for the Central Universities of Central South University (No. 2013zzts082).

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Xiangya Road, Changsha, 410008, Hunan, People’s Republic of China

    Ruixin Li, Weijie Yuan & Zihua Chen

  2. Department of Nephrology, Xiangya Hospital, Central South University, Xiangya Road, Changsha, 410008, Hunan, People’s Republic of China

    Wenjuan Mei

  3. Department of Pathology, Xiangya Hospital, Central South University, Xiangya Road, Changsha, 410008, Hunan, People’s Republic of China

    Keda Yang

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  1. Ruixin Li
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Correspondence to Zihua Chen.

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Li, R., Yuan, W., Mei, W. et al. MicroRNA 520d-3p inhibits gastric cancer cell proliferation, migration, and invasion by downregulating EphA2 expression. Mol Cell Biochem 396, 295–305 (2014). https://doi.org/10.1007/s11010-014-2164-6

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