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MicroRNA-3194-3p inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by decreasing Wnt/β-catenin signaling through targeting BCL9.

Abstract
Local and systemic metastasis of hepatocellular carcinoma (HCC) causes the poor prognosis and increasing evidence confirms that aberrant miRNAs were involved in cancer progression. However, the expression and mechanisms of a specific miR-3194-3p in HCC remains unknown. In this research, we demonstrated that miR-3194-3p, significantly down-regulated in HCC tissues and cell lines, was associated with metastasis and recurrence of HCC. Notably, gain- and loss-of-function assays demonstrated that miR-3194-3p inhibited the migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells in vitro and in vivo. BCL9, up-regulated in HCC tissues, was a direct downstream target of miR-3194-3p and mediated the functional influence of miR-3194-3p. Most importantly, miR-3194-3p exerted its function by regulating β-catenin pathway. Moreover, miR-3194-3p and BCL9 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the down-expression of miR-3194-3p in HCC. Also, the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-3194-3p. Altogether, our study suggested that miR-3194-3p inhibits HCC EMT via decreasing Wnt/β-catenin signaling through targeting BCL9 and might be a therapeutic target for HCC.
AuthorsBowen Yao, Yazhao Li, Liang Wang, Tianxiang Chen, Yongshen Niu, Qingguang Liu, Zhikui Liu
JournalArtificial cells, nanomedicine, and biotechnology (Artif Cells Nanomed Biotechnol) Vol. 47 Issue 1 Pg. 3885-3895 (Dec 2019) ISSN: 2169-141X [Electronic] England
PMID31561723 (Publication Type: Journal Article, Retracted Publication)
Chemical References
  • BCL9 protein, human
  • MIRN3194 microRNA, human
  • MicroRNAs
  • Transcription Factors
Topics
  • Aged
  • Animals
  • Carcinoma, Hepatocellular (genetics, pathology)
  • Cell Line, Tumor
  • Cell Movement (genetics)
  • Down-Regulation (genetics)
  • Epithelial-Mesenchymal Transition (genetics)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms (genetics, pathology)
  • Male
  • Mice
  • MicroRNAs (genetics)
  • Middle Aged
  • Neoplasm Invasiveness (genetics)
  • Neoplasm Metastasis (genetics)
  • Transcription Factors (genetics)
  • Wnt Signaling Pathway (genetics)

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