miR-183-5p Promotes HCC Migration/Invasion via Increasing Aerobic Glycolysis

Yaqian Niu; Fang Liu; Xiuyue Wang; Yuling Chang; Yanmei Song; Huiyuan Chu; Shisan Bao; Che Chen

doi:10.2147/OTT.S304117

miR-183-5p Promotes HCC Migration/Invasion via Increasing Aerobic Glycolysis

Onco Targets Ther. 2021 Jun 4:14:3649-3658. doi: 10.2147/OTT.S304117. eCollection 2021.

Authors

Yaqian Niu¹, Fang Liu¹, Xiuyue Wang¹, Yuling Chang¹, Yanmei Song¹, Huiyuan Chu¹, Shisan Bao², Che Chen¹

Affiliations

¹ Department of Clinical Laboratory Diagnostics, School of Public Health, Gansu University of Chinese Medicine, Lanzhou, Gansu, People's Republic of China.
² Discipline of Pathology, School of Medical Sciences and Bosch Institute, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia.

Abstract

Background: The mortality and morbidity of hepatocellular carcinoma (HCC) are still unacceptably high, despite decades of extensive studies. Aerobic glycolysis is a hallmark of cancer metabolism, closely relating to invasion and metastasis of HCC. MicroRNAs (miRNAs) are involved in the regulation of aerobic glycolysis. miR-183-5p, an oncogenic miRNA, is highly expressed in HCC, but the regulatory mechanism of miR-183-5p in migration, invasion and aerobic glycolysis in HCC remains unclear.

Purpose: To elucidate whether miR-183-5p affects aerobic glycolysis to regulate the migration and invasion of HCC, and to explore its regulatory mechanism.

Methods: We attempted to observe the effects of miR-183-5p on the migration and invasion of HepG2 cells by a wound-healing assay and Transwell assays. The effect of miR-183-5p on glycolysis was determined by glucose uptake and lactate generation. Western blot and qPCR were used to detect the relevant proteins and miRNA expression.

Results: Our results show that miR-183-5p promoted migration and invasion, enhanced glycolysis via increasing glucose uptake and lactate generation, and up-regulated glycolysis-related gene (PKM2, HK2, LDHA, GLUT1) expression in HepG2 cells. Further experiments indicated that miR-183-5p could decrease PTEN expression, but increased Akt, p-Akt and mTOR expression in HepG2 cells.

Conclusion: These findings suggest that miR-183-5p may promote HCC migration and invasion via increasing aerobic glycolysis through targeting PTEN and then activating Akt/mTOR signaling.

Keywords: PTEN/Akt/mTOR; aerobic glycolysis; hepatocellular carcinoma; invasion; miR-183-5p; migration.