miR-124-3p combined with miR-506-3p delay hepatic carcinogenesis via modulating sirtuin 1

Biomarkers. 2021 May;26(3):196-206. doi: 10.1080/1354750X.2020.1854856. Epub 2021 Feb 18.

Abstract

Our study aimed at exploring whether miR-124-3p and miR-506-3p collaboratively modulated sirtuin 1 (SIRT1) protein expression in liver cancer. Materials and methods: In this study, cell viability, migration and invasion were assessed using CCK8 and transwell assays, respectively. Immunohistochemical (IHC) staining and immunoblotting analysis were performed to evaluate SIRT1 protein expression levels in tissue specimens and cell lines. Moreover, the nude-mouse transplanted tumour model was used to assess liver cancer cell growth in vivo. Results: Our results showed that SIRT1 protein levels were significantly up-regulated in liver cancer tissues and cancerous cell lines. Conversely, miR-124-3p and miR-506-3p were down-regulated in liver cancer tissues and cell lines. The protein expression of SIRT1 was significantly declined in HepG2 and SMMC7721 cells after transfection with miR-124-3p or miR-506-3p mimics. miR-124-3p and miR-506-3p collaboratively caused a marked inhibition of liver cancer cell growth, migration and invasion, while the phenomena were neutralized by overexpression of SIRT1. In vivo experimental measurements also revealed that miR-124-3p and miR-506-3p synergistically inhibited SIRT1 protein expression and tumour growth in the nude-mouse transplanted tumour model. Conclusion: It was observed that miR-124-3p and miR-506-3p could cooperatively retard liver cancer cell growth via co-inhibiting SIRT1 protein expression.

Keywords: hepatocellular carcinoma; miR-124-3p; miR-506-3p; prognosis; sirtuin 1.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Tumor Burden

Substances

  • MIRN124 microRNA, human
  • MIRN506 microRNA, human
  • MicroRNAs
  • SIRT1 protein, human
  • Sirtuin 1