MKL1/PINK1-AS/miR-34a-5p Regulates ALDOA to Affect Aerobic Glycolysis in Hepatocellular Carcinoma

Abstract

BackgroundAldolase A, an important metabolic enzyme in the glycolytic pathway, plays an important role in regulating tumour metabolism. In this study, we investigated the expression pattern of ALDOA in hepatocellular carcinoma and its biological role in tumour progression.MethodsBioinformatics analysis, Western Blot and RT-qPCR were performed to detect the relative expression of ALDOA in hepatocellular carcinoma tissues and cell lines. A loss-of-function approach was used to investigate the biological function of ALDOA. The role of ALDOA on glycolysis and apoptosis was assessed by Western Blot, glucose and lactate assay kits, flow cytometry and a nude mouse xenograft model. RNA immunoprecipitation, luciferase reporter experiment, chromatin immunoprecipitation and Western Blot were performed to elucidate the underlying molecular ResultsElevated ALDOA expression correlated with the prognosis of hepatocellular carcinoma patients. exogenous downregulation of ALDOA expression significantly inhibited cellular glycolysis and promoted apoptosis. Mechanistic studies suggest that ALDOA is a direct target of miR-34a-5p, which can enhance apoptosis and inhibit glycolysis in hepatocellular carcinoma cells by targeting the 3'UTR of ALDOA. PINK1-AS competitively sponged miR-34a-5p to increase ALDOA expression by antagonizing miR-34a-5p-mediated ALDOA inhibition. MKL1 acted as a transcription factor to promote the expression of PINK1-AS and ALDOA, thus promoting the deterioration of hepatocellular carcinoma cells.ConclusionThis study shows that high expression of ALDOA contributes to the development and poor prognosis of hepatocellular carcinoma and will be a target and potential prognostic biomarker for the treatment of hepatocellular carcinoma.