MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1 alpha-mediated glycolysis

作者：Chen, Yao; Zhang, Ziqing; Luo, Chengqun; Chen, Zizi; Zhou, Jianda^*

来源：Oncology Reports, 2016, 36(1): 471-479.

DOI：10.3892/or.2016.4824

• malignant melanoma
• microRNA-18b
• proliferation
• glycolysis
• HIF-1 alpha

MicroRNAs (miRs) have been demonstrated to play critical roles in the development and progression of malignant melanoma (MM). However, the exact role and underlying mechanism of miR-18b in MM growth remains unclear. In the present study, real-time PCR data indicated that miR-18b was significantly downregulated in MM tissues compared to their matched adjacent non-tumor tissues. Low miR-18b expression was significantly associated with the tumor thickness and stage, although no significant association was observed between the miR-18b expression and the age, gender, or lymph node metastasis. Besides, miR-18b was also significantly downregulated in MM B16 and A375 cells compared to normal skin HACAT cells. Ectopic expression of miR-18b decreased the proliferation of A375 and B16 cells, while induced a remarkable cell cycle arrest at 01 stage. Besides, miR-18b overexpression also inhibited the glycolysis in A375 and B16 cells. HIF-1 alpha, a key regulator in glycolysis, was then identified as a target gene of miR-18b, and its expression was negatively mediated by miR-18b in A375 and B16 cells. Overexpression of HIF-1 alpha rescued the suppressive effect of miR-18b on MM cell proliferation and glycolysis. In vivo study further showed that overexpression of miR-18b inhibited the MM growth as well as the tumor-related death, accompanied with HIF-1 alpha downregulation. Taken together, the present study suggests that miR-18b inhibits the growth of MM cells in vitro and in vivo through directly targeting HIF-1 alpha.

• 出版日期2016-7
• 单位中南大学