title: MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1α-mediated glycolysis.
abstract: 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 G1 stage. Besides, miR-18b overexpression also inhibited the glycolysis in A375 and B16 cells. HIF-1α, 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-1α 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-1α 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-1α.
authors.affiliation: Department of Plastic and Cosmetic Surgery, Longgang Orthopetics Hospital of Shenzhen, Shenzhen, Guangdong 518000. P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Plastic and Cosmetic Surgery, Longgang Orthopetics Hospital of Shenzhen, Shenzhen, Guangdong 518000. P.R. China.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Plastic Surgery, the Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Chengqun
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Plastic Surgery, the Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Zizi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Plastic Surgery, the Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jianda
authors.initials: J
authors.lastname: Zhou
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D016193:G1 Phase / Q000235:genetics; D006019:Glycolysis / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008546:Melanoma, Experimental / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015398:Signal Transduction / Q000235:genetics
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C581632:MIRN18 microRNA, human; D035683:MicroRNAs