LINC00052/miR-101-3p axis inhibits cell proliferation and metastasis by targeting SOX9 in hepatocellular carcinoma

Gene. 2018 Dec 30:679:138-149. doi: 10.1016/j.gene.2018.08.038. Epub 2018 Aug 8.

Abstract

Long non-coding RNAs (lncRNAs) have emerged as critical regulators in a variety of diseases, including many tumors, such as hepatocellular carcinoma (HCC). However, the function and mechanisms responsible for these molecules in HCC are not thoroughly understood. In our previous study, we found that LINC00052 was acted as a tumor suppressor in HCC. In this study, we performed transcription microarray analysis to investigate the target gene of LINC00052, and found that knockdown of LINC00052 significantly increased the expression of SRY-related HMG-box gene 9 (SOX9), which plays an oncogenic role in HCC. Moreover, luciferase reporter assay revealed that LINC00052 promoted miR-101-3p expression by enhancing its promoter activity. In addition, online database analysis tools and luciferase assays showed that miR-101-3p could target SOX9. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that miR-101-3p was downregulated in HCC tissues and HCC cell lines. And we found a positive relationship between LINC00052 and miR-101-3p, and a negative relationship between miR-101-3p and SOX9 in HCC tissues. Besides, miR-101-3p was involved in LINC00052 inhibits HCC cells proliferation and metastasis. At the molecular level, LINC00052 downgulated SOX9 to inhibit HCC cells proliferation and metastasis by interacting with miR-101-3p. It might be a potential application for HCC therapy.

Keywords: HCC; LINC00052; Metastasis; Proliferation; SOX9; miR-101-3p.

MeSH terms

  • 3' Untranslated Regions
  • Carcinoma, Hepatocellular / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • MicroRNAs / genetics*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding / genetics*
  • SOX9 Transcription Factor / genetics*

Substances

  • 3' Untranslated Regions
  • MIRN101 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SOX9 Transcription Factor
  • SOX9 protein, human