J Cancer 2021; 12(4):1144-1153. doi:10.7150/jca.43379 This issue
Department of Hepato-Biliary-Pancreatic and Vascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
Purpose: Various studies have identified miR-202 critically participated in the development of different cancers. However, the potential mechanisms underlying the carcinogenesis of pancreatic cancer (PC) still remains elusive.
Methods: In the study, cell proliferation assay, colony formation assay, EdU incorporation assay, Luciferase reporter assay, lactate production, glucose consumption assay, real-time PCR and western blot were used to investigate the mechanism of hexokinase 2 (HK2) regulated by miR-202 in pancreatic cancer in vitro and in vivo.
Results: Here we found that miR-202 was decreased in the PC tissues, and its low expression was correlated with a poor prognosis of PC patients. Overexpression of miR-202 in PC cells reduced cell proliferation and tumorigenesis by impairing glycolysis, while downregulation of miR-202 promoted the cells proliferative capacity. Mechanically, we demonstrated that HK2, an enzyme that catalyzes the irreversible rate-limiting step of glycolysis, as the direct target of miR-202. Overexpression of miR-202 suppressed both the mRNA and protein levels of HK2, whereas re-introduction of HK2 abrogated miR-202-mediated glycolytic inhibition. In addition, the expression of miR-202 was negatively associated with HK2 level in a cohort of PC tissues.
Conclusion: Our findings validate the mechanism that miR-202 reprograms the metabolic process to promote PC progression, thus providing potential prognostic predictors for PC patients.
Keywords: miR-202, Hexokinase 2, Glycolysis, Pancreatic cancer