Overexpression of miR-181a regulates the Warburg effect in triple-negative breast cancer. (2nd January 2023)

• Record Type: Journal Article
• Authors: Wang, Y.; Tahiri, H.; Yang, C.; Gu, M.; Ruan, X.; Hardy, P.
• Is Part Of: Climacteric. Volume 26:Number 1(2023)
• Page Start: 64
• Page End: 71
• Publication Date: 2023-01-02
• Subjects: Triple-negative breast cancer -- miR-181a -- Warburg effect -- glycolysis -- AKT3 -- PGRMC1; Menopause -- Periodicals; Menopause -- Hormone therapy -- Periodicals; Menopause -- Periodicals; Estrogen Replacement Therapy -- Periodicals; Gynecology -- Periodicals; Societies, Medical -- Periodicals; 612.665
• DOI: 10.1080/13697137.2022.2147821
• Languages: English
• ISSNs: 1369-7137

Abstract

Abstract: Objective: Triple-negative breast cancer (TNBC) is highly aggressive and leads to a poor prognosis. microRNA-181a (miR-181a) exhibits strong antineoplastic effects in many types of cancer. In this study, we examine the responses of human miR-181a-transfected TNBC cells and explore the mechanisms underlying the observed effects. Methods: A series of cellular assays were conducted using cells from the MDA-MB-231 TNBC line to assess the impact of miR-181a overexpression. The extracellular acidification rate, lactate production and glucose uptake were evaluated as a measure of aerobic glycolysis (i.e. the Warburg effect). The expressions of glycolysis-related gene were analyzed. Results: Viability, migration and survival of miR-181a-transfected MDA-MB-231 cells were all significantly reduced. miR-181a inhibited glycolysis in TNBC cells by reducing the rates of glucose uptake and lactate production and a substantial downregulation of factors known to contribute to the Warburg effect, including the serine/threonine kinase, AKT3, hypoxia-inducible factor-1α (HIF-1α) and progesterone receptor membrane component 1 (PGRMC1). Conclusion: Our results demonstrate that miR-181a may regulate glycolysis in MDA-MB-231 TNBC cells, potentially via interference with components of the AKT3–HIF-1α and PGRMC1 pathways. These results suggest that miR-181a might be developed as a therapeutic agent for use in antineoplastic regimens directed at TNBC and PGRMC1-overexpressing breast cancers.