title: miR-33a functions as a tumor suppressor in melanoma by targeting HIF-1α.
abstract: BACKGROUND
  Our previous findings showed that miR-33 expressed abnormally in clinical specimens of melanoma, but the exact molecular mechanism has not been elucidated.
  
  
  OBJECTIVE
  To determine miR-33's roles in melanoma and confirm whether HIF-1α is a direct target gene of miR-33a.
  
  
  METHODS
  First miR-33a/b expression levels were detected in HM, WM35, WM451, A375 and SK-MEL-1. Then lentiviral vectors were constructed to intervene miR-33a expression in melanoma cells. Cell proliferation, invasion and metastasis were detected. A375 cells mice model was performed to test the tumorigenesis of melanoma in vivo. Finally the dual reporter gene assay was carried out to confirm whether HIF-1α is a direct target gene of miR-33a.
  
  
  RESULTS
  MiR-33a/b exhibited a lower expression in WM35, WM451, A375 and SK-MEL-1 of the metastatic skin melanoma cell lines than that in HM. Then inhibition of miR-33a expression in WM35 and WM451 cell lines could promote cell proliferation, invasion and metastasis. Conversely, increased expression of miR-33a in A375 cells could inhibit cellproliferation, invasion and metastasis. In vivo tests also confirmed that overexpression of miR-33a in A375 cells significantly inhibited melanoma tumorigenesis. Finally, we confirmed that HIF-1α is a direct target gene of miR-33a.
  
  
  CONCLUSIONS
  The newly identified miR-33a/HIF-1α axis might provide a new strategy for the treatment of melanoma.
authors.affiliation: a Department of Plastic Surgery ; Third Xiangya Hospital; Central South University ; Changsha City , China.
authors.forename: Jianda
authors.initials: J
authors.lastname: Zhou
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Huiqing
authors.initials: H
authors.lastname: Xie
authors.forename: Jingtian
authors.initials: J
authors.lastname: Tang
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Shaohua
authors.initials: S
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Quanyong
authors.initials: Q
authors.lastname: He
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Peiguo
authors.initials: P
authors.lastname: Cao
authors.forename: Ke
authors.initials: K
authors.lastname: Cao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D023041:Xenograft Model Antitumor Assays
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C550416:MIRN33a microRNA, human; D035683:MicroRNAs
keywords: HIF-1α; HIF-1α, hypoxia inducible factor 1, α subunit; cell proliferation; invasion; melanoma; metastasis; miR-33a; miR-33a/b, microRNA 33a/b; microRNAs