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

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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.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by AAN, EE-Ah and EE-Z. The first draft of the manuscript was written by AAN, HS and SA, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hanan Saleh.

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The authors report no conflicts of interest in this work.

Ethical approval

The present study has been waived from ethical permissions from Institutional Animal Care and Use Committee (IACUC), Faculty of Science, Cairo University (Egypt). All applicable international, national, and/or institutional guidelines for care and use of cell lines were followed.

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Nabi, A.A., Atta, S.A., El-Ahwany, E. et al. Taurine Upregulates miRNA-122-5p Expression and Suppresses the Metabolizing Enzymes of Glycolytic Pathway in Hepatocellular Carcinoma. Mol Biol Rep 48, 5549–5559 (2021). https://doi.org/10.1007/s11033-021-06571-y

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