J Cancer 2021; 12(4):1144-1153. doi:10.7150/jca.43379 This issue

Research Paper

MicroRNA-202 suppresses glycolysis of pancreatic cancer by targeting hexokinase 2

Shuang-Jia Wang, Xiu-Dong Li, Lu-Peng Wu, Ping Guo, Liu-Xing Feng, Bin Li

Department of Hepato-Biliary-Pancreatic and Vascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China

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Wang SJ, Li XD, Wu LP, Guo P, Feng LX, Li B. MicroRNA-202 suppresses glycolysis of pancreatic cancer by targeting hexokinase 2. J Cancer 2021; 12(4):1144-1153. doi:10.7150/jca.43379. Available from https://www.jcancer.org/v12p1144.htm

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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