MicroRNA-199a-5p inhibits tumor proliferation in melanoma by mediating HIF-1α.
The expression of hypoxia-inducible factor 1α (HIF-1α) is often abundant in human cancer and it is associated with poor prognosis. The present study aimed to investigate its regulation by microRNA (miRNA). The expression of miRNA-199a-5p (miR-199a-5p) in melanoma was detected by quantitative polymerase chain reaction on samples from 25 melanoma patients. The target of miR-199a-5p was predicted and demonstrated by a dual‑luciferase reporter system. The effects of miR-199a-5p on melanoma cells were assayed in B16 and HME1 melanoma cell lines. Furthermore, the potential of miR‑199a‑5p as a therapeutic target was illustrated in xenograft nude mice models. Low expression of miR‑199a‑5p in tumor melanoma tissue samples from patients was associated with high histological grade and advanced tumor stage. The 3'-untranslated region of HIF‑1α was identified as a target of miR‑199a‑5p by Targetscan software. The dual-luciferase reporter assay demonstrated that miR‑199a‑5p transfection of mimics decreased the luciferase activity significantly (P<0.05). In the B16 and HME1 cell lines, overexpression of miR‑199a‑5p suppressed cell proliferation and arrested the cell cycle in the G1 phase. In vivo overexpression of miR‑199a‑5p significantly suppressed xenograft growth and downregulated the expression of HIF‑1α (P<0.05). The results from the present study suggest that miR‑199a‑5p suppressed melanoma proliferation via HIF‑1α, suggesting it may be a potential therapeutic target for melanoma treatment.
Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Xinghua
X
Yang
Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Shaorong
S
Lei
Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Jianhong
J
Long
Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Xiaojin
X
Liu
Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Qizhen
Q
Wu
D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C531408:mirn199 microRNA, human