MiR‑185 regulates the growth of osteosarcoma cells via targeting Hexokinase 2.

Abstract

MicroRNAs (miRNAs) have been proposed as potential prognostic and diagnostic biomarkers in numerous types of cancer, including osteosarcoma (OS), which is the most common bone malignancy. The present study revealed that the expression of miR-185 was downregulated in OS tissues and cells. Overexpression of miR-185 significantly suppressed the proliferation and migration of OS cells. To further investigate the functional roles of miR-185 in OS, the downstream targets of miR-185 were predicted using the microRNA.org database. The results revealed that in cancer cells, hexokinase 2 (HK2), the rate-limiting enzyme of glycolysis, was a potential target of miR-185. Molecular analysis indicated that miR-185 binds to the 3′-untranslated region of HK2 mRNA. Overexpressed miR-185 downregulated the mRNA and protein levels of HK2 in OS cells. In addition, an inverse correlation between the expression of miR-185 and HK2 was reported in OS. Consistent with the downregulation of HK2 induced by miR-185, overexpression of HK2 in OS cells significantly attenuated the inhibitory effects of miR-185 on glucose consumption and lactate production, while depletion of miR-185 promoted the glycolysis of OS cells. Additionally, restoration of HK2 abolished the inhibitory effects of miR-185 on the proliferation of OS cells. In summary, these results revealed that miR-185 suppressed the glucose metabolism of OS cells; thus, miR-185 may be considered as a promising therapeutic target for the treatment of OS.