miR-500a-3p/CDK6 Axis Suppresses Aerobic Glycolysis in Colorectal Cancer

Abstract Backgrounds Colorectal cancer (CRC) is one of the cancers with the highest mortality rate and understanding the mechanism behind its progression is the key to improve patients’ prognosis. The role of miR-500a-3p has been demonstrated to be involved in the progression of several human cancers but its role in CRC is unclear. The aim of this study was to disclose the function of miR-500a-3p in CRC progression. Methods The expression of miR-500a-3p and Cyclin-dependent kinases 6 (CDK6) in 134 CRC tissues were tested respectively. The effects on cell proliferation by miR-500a-3p were explored in vitro and in vivo. The glycolysis of CRC cells was determined by Mass Spectrometry and Seahorse XF 96 Extracellular Flux Analyzer. Dual-luciferase reporter assay were performed to validate the relationship between miR-500a-3p and CDK6. Results miR-500a-3p was abnormally down-regulated in CRC tissues and cell lines and was negatively associated with malignancies and worse prognosis. miR-500a-3p mimics impeded CRC cells proliferation in vitro and in vivo. miR-500a-3p inhibited glucose consumption, lactate and ATP production, down-regulated the expression of hexokinase2 (HK2). Bioinformatics database prediction combined with western blot and luciferase assay confirmed that CDK6 is the direct target of miR-500a-3p. CDK6 overexpression was able to rescue the inhibitory function of miR-500a-3p on the proliferation and glycolysis in CRC cells. Conclusions The results of this study reveal a potential tumor suppressor role of miR-500a-3p by inhibiting proliferation and aerobic glycolysis through targeting CDK6 in CRC, which may provide new insights into novel prognostic biomarker and therapeutic targets for CRC.