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Deregulation of miR-520d-3p promotes hepatocellular carcinoma development via lncRNA MIAT regulation and EPHA2 signaling activation.

Abstract
MicroRNA-520d-3p (miR-520d-3p) is a novel cancer-related miRNA and functions as a tumor suppressor in human cancers. However, the expression patterns and mechanisms of miR-520d-3p involved in hepatocellular carcinoma (HCC) remain rarely known. Here, we found that the expression levels of miR-520d-3p in HCC tissues and cells were significantly lower than in tumor-adjacent tissues and L02 cells. Decreased level of miR-520d-3p was relevant to poor overall survival, whereas miR-520d-3p up-regulation resulted in a marked inhibition of cell growth, migration and invasion. In addition, the long non-coding RNA, myocardial infarction associated transcript (MIAT) was up-regulated in both HCC tissues and cell lines. MIAT suppressed the expression and function of miR-520d-3p. Moreover, erythropoietin-producing hepatocellular A2 (EPHA2) was speculated and confirmed as a direct target of miR-520d-3p. We also demonstrated that MIAT may function as a sponge competitive endogenous RNA for miR-520d-3p, and thus regulate the molecular expression of EPHA2. In summary, our study has identified a novel signaling pathway through which miR-520d-3p exerts its anticarcinogenic roles and suggested that the MIAT/miR-520d-3p/EPHA2 may be a new target for HCC therapy.
AuthorsYun Xiang, Yongguo Huang, Hong Sun, Yang Pan, Min Wu, Jiayun Zhang
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 109 Pg. 1630-1639 (Jan 2019) ISSN: 1950-6007 [Electronic] France
PMID30551417 (Publication Type: Journal Article)
CopyrightCopyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Chemical References
  • EPHA2 protein, human
  • Ephrin-A2
  • MIRN520 microRNA, human
  • Miat long non-coding RNA
  • MicroRNAs
  • RNA, Long Noncoding
  • Receptor, EphA2
Topics
  • Adult
  • Carcinoma, Hepatocellular (metabolism, pathology)
  • Cell Line, Tumor
  • Ephrin-A2 (biosynthesis)
  • Female
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms (metabolism, pathology)
  • Male
  • MicroRNAs (biosynthesis)
  • Middle Aged
  • RNA, Long Noncoding (physiology)
  • Receptor, EphA2
  • Signal Transduction (physiology)

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