CircRBM33 Downregulation Inhibits Hypoxia-induced Glycolysis and Promotes Apoptosis of Breast Cancer Cells Via a MicroRNA-542-3p/HIF-1α Axis

Overview

Journal Cell Death Discov

Date 2022 Mar 23

PMID 35318311

Authors

Yiming Jiang

Meiqi Zhang

Danlu Yu

Guoxin Hou

Jingyi Wu

Fuming Li

Affiliations

Soon will be listed here.

Abstract

Many circRNAs are involved in the carcinogenesis of breast cancer (BCa) through the transcription of microRNAs (miRNAs) and mRNAs. This study investigated circRBM33 regulation of the miR-542-3p/hypoxia-inducible factor-1α (HIF-1α) axis in BCa. BCa clinical tissue samples were collected to test differential expressions of circRBM33, miR-542-3p, and HIF-1α. MCF-7 cells were subjected to normoxia or hypoxia and transfected with plasmids that regulated CircRBM33, miR-542-3p, and HIF-1α expression levels. Glycolysis was evaluated by measuring glucose consumption, lactic acid production, and protein expression of hexokinase 2, glucose transporter type 1 and lactic dehydrogenase A. Cell proliferation and apoptosis were also assessed, and the interactions between genes were explored. CircRBM33 and HIF-1α were upregulated, while miR-542-3p was downregulated in BCa tissue samples and cell lines. Hypoxia induced circRBM33 expression in BCa cells, which negatively regulated miR-542-3p expression. CircRBM33 knockdown or miR-542-3p rescue reduced glycolysis and proliferation and promoted apoptosis of BCa cells. MiR-542-3p inhibition rescued circRBM33 knockdown-mediated glycolysis, proliferation and apoptosis of BCa cells. MiR-542-3p targeted HIF-1α, and the overexpression of HIF-1α reversed the effect of miR-542-3p upregulation on glycolysis, proliferation, and apoptosis of BCa cells. Collectively, downregulating circRBM33 suppresses miR-542-3p-targeted HIF-1α expression, resulting in the inhibition of glycolysis and proliferation and the promotion of BCa cells' apoptosis.

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