Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

MicroRNA-124 Enhances T Cells Functions by Manipulating the Lactic Acid Metabolism of Tumor Cells

Tue Apr 16 08:41:29 2024

(2023) MicroRNA-124 Enhances T Cells Functions by Manipulating the Lactic Acid Metabolism of Tumor Cells. Iranian Journal of Allergy Asthma and Immunology. pp. 62-71. ISSN 1735-1502

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Official URL: <Go to ISI>://WOS:000942586400006

Abstract

High production of lactic acid is a common feature of various tumors. Lactic acid is an immunosuppressive molecule with crucial roles in tumor cells' immune escape, which could largely be attributed to its negative effects on the T cells present in the tumor microenvironment (TME). Strategies that decrease the glycolysis rate of tumor cells could enhance immunosurveillance and limit tumor growth. Pyruvate kinase M2 (PKM2) is a key enzyme in the glycolysis pathway, and it plays a vital role in lactic acid buildup in the TME. MicroRNA (miR)-124 has been shown to be able to decrease tumor cell lactic acid synthesis indirectly by reducing PKM2 levels.In this study, we first overexpressed miR-124 in the tumor cells and evaluated its effects on the PKM2 expression and lactic acid production of the tumor cells using quantitative real-time polymerase chain reaction (qRT-PCR) and spectrophotometry, respectively. Then, we cocultured miR-124-treated tumor cells with T cells to investigate the effects of miR-124 overexpression on T cell proliferation, cytokine production, and apoptosis.Our results demonstrated that miR-124 overexpression could significantly reduce the amount of lactic acid produced by tumor cells by manipulating their glucose metabolism, which led to the augmented proliferation and IFN-gamma production of T cells. Moreover, it rescued T cells from lactic acid-induced apoptosis.Our data suggest that lactic acid is a hindering factor for T-cell-based immunotherapies; however, manipulating tumor cells' metabolism via miR-124 could be a promising way to improve antitumor responses of T cells.

Item Type: Article
Creators:
CreatorsEmail
Khakpoor-Koosheh, M.UNSPECIFIED
Rostamian, H.UNSPECIFIED
Masoumi, E.UNSPECIFIED
Jafarzadeh, L.UNSPECIFIED
Fallah-Mehrjardi, K.UNSPECIFIED
Tavassolifar, M. J.UNSPECIFIED
Noorbakhsh, F.UNSPECIFIED
Mirzaei, H. R.UNSPECIFIED
Hadjati, J.UNSPECIFIED
Rezaei, N.UNSPECIFIED
Keywords: Lactic acid Metabolism MIRN124 microRNA human T-lymphocytes Tumor microenvironment high lactate levels pyruvate-kinase cancer metastases isoform predict growth head Allergy Immunology
Divisions:
Page Range: pp. 62-71
Journal or Publication Title: Iranian Journal of Allergy Asthma and Immunology
Journal Index: ISI
Volume: 22
Number: 1
Identification Number: https://doi.org/10.18502/ijaai.v22i1.12007
ISSN: 1735-1502
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/4217

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