title: miRNA-34a suppresses cell proliferation and metastasis by targeting CD44 in human renal carcinoma cells.
abstract: OBJECTIVE
  We investigated the potential functions of miR-34a in CD44 transcriptional complexes in renal cell carcinoma.
  
  
  METHODS
  We detected miR-34a expression by quantitative real-time polymerase chain reaction. Oligonucleotides were used to over express miR-34a. Cell proliferation and xenograft assays, colony formation and flow cytometry were done to examine effects on cancer cell proliferation in vitro and in vivo. Luciferase assay was performed to verify the precise target of miR-34a.
  
  
  RESULTS
  Promoter methylation contributed to miR-34a loss in the ACHN, 786-O and SN12PM6 renal carcinoma cell lines. Ectopic over expression of miR-34a restrained cell growth, tube formation and migration/invasion, and significantly suppressed the growth of renal carcinoma xenografts and metastasis in nude mice. Dual luciferase assay revealed that CD44 was a direct target of miR-34a in renal cancer cells and CD44 knockdown by RNAi in renal cancer cells suppressed tumor progression. In contrast, CD44 ectopic expression partially reversed the antitumor effects of miR-34a in renal cancer cells.
  
  
  CONCLUSIONS
  Our findings indicate that miR-34a targets CD44 in renal cancer cells and suppresses renal cancer cell growth, tube formation and metastasis in vitro and in vivo. Thus, miR-34a may be a potential molecular target for novel therapeutic strategies for clear cell renal carcinoma.
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Gan
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cell Death and Cancer Genetics, The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania.
authors.forename: Kiranmai
authors.initials: K
authors.lastname: Gumireddy
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania.
authors.forename: Anping
authors.initials: A
authors.lastname: Li
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tang
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Haibing
authors.initials: H
authors.lastname: Xiao
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lang
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. Electronic address: xuhuawhu@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000276:immunology / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009374:Neoplasms, Experimental; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018960:Hyaluronan Receptors; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D012334:RNA, Neoplasm
keywords: CD44 protein; MIRN34 microRNA; carcinogenesis; carcinoma; human; kidney; renal cell