Taurine Upregulates miRNA-122-5p Expression and Suppresses the Metabolizing Enzymes of Glycolytic Pathway in Hepatocellular Carcinoma

Mol Biol Rep. 2021 Jul;48(7):5549-5559. doi: 10.1007/s11033-021-06571-y. Epub 2021 Jul 27.

Abstract

Background: Hepatocellular carcinoma (HCC) is a complicated disease with a poor prognosis and high mortality rates. The prevention, control, diagnosis, and treatment of liver cancer have become vital focuses in healthcare research.

Aim: This study aimed to evaluate the in vitro effect of taurine (Tau) on the expression of miR-122-5p that targets some limiting glycolytic enzymes and affects the overall glycolytic pathway in HepG2 cells.

Method: IC50 and the inhibitory effect of Tau on cell proliferation were measured after 48 h by MTT assay. Then, the mRNA expressions of some apoptosis-related genes P53, BAX, Caspase-3, and Bcl-2 were measured using quantitative real-time (qRT-PCR) and the protein levels were confirmed by enzyme-linked immunosorbent assay (ELISA). The activities of some antioxidant's biomarkers were assessed. The gene expression of miR-122-5p that targets some limiting glycolytic enzymes; Aldolase and Lactate dehydrogenase (LDH), were evaluated after treatment with Tau for 48 h.

Results: A Significant inhibition in the proliferation of HepG2 was encountered after treatment with Tau in a dose-dependent manner. Moreover, the expression of apoptotic genes p53, Bax, and Caspase-3 exhibited a significant upregulation, while Bcl-2 showed a significant downregulation. These alterations in the expression levels were also confirmed on the protein level. The antioxidant activities of GPx, CAT, and NO were significantly elevated versus untreated control. Also, a significant increase in the expression level of miR-122-5p was observed after treatment with Tau affecting the metabolic activity of HCC cells. Concomitantly, a significant inhibition in ALDOA protein and the hallmark of glycolytic enzymes LDH and Aldolase were observed.

Conclusions: These observations showed that taurine inhibits HepG2 cell proliferation and restores the expression of miR-122-5p which inhibits the hallmark glycolytic enzymes and ultimately the metabolic activity of HCC cells. Tau is assumed to be a promising and effective antitumor therapy of HCC.

Keywords: Antioxidants; Apoptotic genes; Glycolytic enzymes; Hepatocellular carcinoma; MicroRNA 122b-5p; Taurine.

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Energy Metabolism / genetics*
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glycolysis / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Metabolic Networks and Pathways / genetics
  • MicroRNAs / genetics*
  • Taurine / pharmacology*

Substances

  • Biomarkers, Tumor
  • MIRN122 microRNA, human
  • MicroRNAs
  • Taurine