miR-145 inhibits aerobic glycolysis and cell proliferation of cervical cancer by acting on MYC
FASEB JOURNAL(2023)
Abstract
Nearly half a million women are diagnosed with cervical cancer (CC) each year, with the incidence of CC stabilizing or rising in low-income and middle-income countries. Cancer cells use metabolic reprogramming to meet the needs of rapid proliferation, known as the Warburg effect, but the mechanism of the Warburg effect in CC remains unclear. microRNAs (miRNAs) have a wide range of ef-fects on gene expression and diverse modes of action, and they regulate genes for metabolic reprogramming. Dysregulation of miRNA expression leads to meta-bolic abnormalities in tumor cells and promotes tumorigenesis and tumor pro-gression. In this study, we found that miR- 145 was negatively correlated with metabolic reprogramming-related genes and prevented the proliferation and me-tastasis of CC cell lines by impeding aerobic glycolysis. A dual-luciferase reporter assay showed that miR- 145 can bind to the 3'-untranslated region (3'- UTR) of MYC. Chromatin Immunoprecipitation-quantitative real -time PCR indicated that MYC was involved in the regulation of glycolysis-related genes. In addition, miR- 145 mimics significantly suppressed the growth of CC cell xenograft tumor, prolonged the survival time of mice, and dramatically silenced the expression of tumor proliferation marker Ki- 67. Therefore, the results suggested that miR- 145 affects aerobic glycolysis through MYC, which may be a potential target for the treatment of CC.
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Key words
cervical cancer,glycolysis,miR-145,MYC,the Warburg effect
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