ROCK2 Promotes Osteosarcoma Growth and Glycolysis by Up-Regulating HKII via Phospho-PI3K/AKT Signalling

Binbin Deng,1,* Jianyong Deng,1,* Xuan Yi,1 Yeqing Zou,2 Chen Li1 1Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Province Key Laboratory of Molecular Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen LiDepartment of Orthopedics, Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi Province 330006, People’s Republic of ChinaEmail tanzikoulc@163.comYeqing ZouJiangxi Province Key Laboratory of Molecular Medicine, Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi Province 330006, People’s Republic of ChinaEmail zouyeqing3366@163.comBackground: Osteosarcoma (OS) is a malignant bone tumour that exhibits a high mortality. While tumours thrive in a state of malnutrition, the mechanism by which OS cells adapt to metabolic stress through metabolic reprogramming remains unclear.Methods: We analysed the expression of ROCK2 in osteosarcoma tissues by RT-qPCR and Western blot. Cell proliferation were analysed using CCK8, EdU and colony formation assays. The level of cell glycolysis was detected by glucose-6 phosphate, glucose consumption, lactate production and ATP levels.Results: Herein, our study showed that ROCK2 expression in OS tissues was higher than in adjacent tissues. Functional assays have demonstrated that ROCK2 contributes to the growth of OS cells by inducing aerobic glycolysis. The current study revealed that ROCK2 knockdown decreased the levels of mitochondrial hexokinase II (HKII). And also indicated that ROCK2 served as a key enzyme in glycolysis and that it served an important role in tumour growth. A significant positive correlation was identified between the mRNA and protein expressions of ROCK2 and HKII, further demonstrating that ROCK2-induced glycolysis and proliferation was dependent on HKII expression in OS cells. Mechanistically, ROCK2 promotes HKII expression by activating the phospho-PI3K/AKT signalling pathway.Conclusion: Taken together, the results of the current study linked the two drivers of OS growth and aerobic glycolysis and identified a new mechanism of ROCK2 control in OS.Keywords: ROCK2, HKII, osteosarcoma, proliferation, glycolysis