Long non-coding RNA DLX6-AS1 aggravates hepatocellular carcinoma carcinogenesis by modulating miR-203a/MMP-2 pathway

Biomed Pharmacother. 2017 Dec:96:884-891. doi: 10.1016/j.biopha.2017.10.056. Epub 2017 Nov 6.

Abstract

Long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigenesis, especially hepatocellular carcinoma (HCC). In present study, our team aims to investigate the role of lncRNA DLX6-AS1 in the HCC carcinogenesis. Results of early-stage experiments found that DLX6-AS1 expression level was up-regulated in 60 cases of HCC tissue samples compared with adjacent normal tissue. Moreover, the aberrant overexpression of DLX6-AS1 indicated the poor prognosis of HCC patients. Loss-of-function experiments revealed that DLX6-AS1 knockdown inhibited the proliferation, migration and invasion of HCC cells in vitro, and decreased the tumor growth in vivo. Bioinformatics analysis predicted that miR-203a potentially targeted DLX6-AS1 3'-UTR, suggesting the interaction between miR-203a and DLX6-AS1. Furthermore, miR-203a also targeted MMP-2 mRNA 3'-UTR, which was validated by luciferase reporter assay. Taken together, our study discovered the oncogenic role of DLX6-AS1 in clinical specimens and cellular experiments, showing the potential DLX6-AS1/miR-203a/MMP-2 pathway. This results and findings provide a novel insight for HCC tumorigenesis.

Keywords: DLX6-AS1; Hepatocellular carcinoma; Long non-coding RNA; MMP-2; miR-203a.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Hep G2 Cells
  • Homeodomain Proteins / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Matrix Metalloproteinase 2 / genetics*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Up-Regulation / genetics

Substances

  • 3' Untranslated Regions
  • DLX6 protein, human
  • Homeodomain Proteins
  • MIRN203 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Matrix Metalloproteinase 2