MicroRNA-363-3p is downregulated in hepatocellular carcinoma and inhibits tumorigenesis by directly targeting specificity protein 1

Mol Med Rep. 2017 Aug;16(2):1603-1611. doi: 10.3892/mmr.2017.6759. Epub 2017 Jun 13.

Abstract

microRNAs exhibit important regulatory roles in tumorigenesis and tumor development, such as in hepatocellular carcinoma (HCC). The present study aimed to investigate the expression and functional roles of microRNA (miR)‑363‑3p in HCC. miR-363-3p expression levels in a number of HCC tissues and cell lines were measured by reverse transcription-quantitative PCR (RT‑qPCR). The effects of miR‑363‑3p expression on HCC cell proliferation, migration and invasion were exa-mined by MTT assay, Transwell migration and invasion assay, respectively. The effects of miR‑363‑3p on its downstream target gene, specificity protein 1 (SP1), were examined by bioinformatics analysis, luciferase reporter assay, RT‑qPCR and western blotting. An SP1 overexpression vector was subsequently transfected into HCC cells to assess any selective effects on miR‑363‑3p in modulating HCC. The results revealed that miR‑363‑3p expression levels were downregulated in both HCC tissues and cell lines, and this low expression level was correlated with tumor size, tumor‑node‑metastasis stage and venous infiltration in patients with HCC. Upregulation of miR‑363‑3p inhibited cell proliferation, migration and invasion in HCC cell cultures. In HCC cells transfected with an SP1 expression vector the miR‑363‑3p‑induced tumor suppressive roles on cell proliferation, migration and invasion were reversed. In conclusion, results from the present study indicated that miR‑363‑3p is a tumor suppressor in HCC and functions through a mechanism involving SP1, suggesting that miR‑363‑3p may be a potential new therapeutic target for the treatment of HCC.

MeSH terms

  • Carcinogenesis / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Down-Regulation
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Transfection

Substances

  • MIRN363 microRNA, human
  • MicroRNAs
  • Sp1 Transcription Factor
  • SP1 protein, human