title: MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth.
abstract: OBJECTIVE
  Prostate cancer (PCa) is characterized by deregulated expression of several tumor suppressor or oncogenic miRNAs. The objective of this study was the identification and characterization of miR-let-7c as a potential tumor suppressor in PCa.
  
  
  METHODS
  Levels of expression of miR-let-7c were examined in human PCa cell lines and tissues using qRT-PCR and in situ hybridization. Let-7c was overexpressed or suppressed to assess the effects on the growth of human PCa cell lines. Lentiviral-mediated re-expression of let-7c was utilized to assess the effects on human PCa xenografts.
  
  
  RESULTS
  We identified miR-let-7c as a potential tumor suppressor in PCa. Expression of let-7c is downregulated in castration-resistant prostate cancer (CRPC) cells. Overexpression of let-7c decreased while downregulation of let-7c increased cell proliferation, clonogenicity and anchorage-independent growth of PCa cells in vitro. Suppression of let-7c expression enhanced the ability of androgen-sensitive PCa cells to grow in androgen-deprived conditions in vitro. Reconstitution of Let-7c by lentiviral-mediated intratumoral delivery significantly reduced tumor burden in xenografts of human PCa cells. Furthermore, let-7c expression is downregulated in clinical PCa specimens compared to their matched benign tissues, while the expression of Lin28, a master regulator of let-7 miRNA processing, is upregulated in clinical PCa specimens.
  
  
  CONCLUSIONS
  These results demonstrate that microRNA let-7c is downregulated in PCa and functions as a tumor suppressor, and is a potential therapeutic target for PCa.
authors.affiliation: Department of Urology, University of California Davis, Sacramento, California, United States of America. nnadiminty@ucdavis.edu
authors.forename: Nagalakshmi
authors.initials: N
authors.lastname: Nadiminty
authors.forename: Ramakumar
authors.initials: R
authors.lastname: Tummala
authors.forename: Wei
authors.initials: W
authors.lastname: Lou
authors.forename: Yezi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xu-Bao
authors.initials: XB
authors.lastname: Shi
authors.forename: June X
authors.initials: JX
authors.lastname: Zou
authors.forename: Hongwu
authors.initials: H
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Xinbin
authors.initials: X
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.forename: Ralph W
authors.initials: RW
authors.lastname: deVere White
authors.forename: Hsing-Jien
authors.initials: HJ
authors.lastname: Kung
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Evans
authors.forename: Allen C
authors.initials: AC
authors.lastname: Gao
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: D000728:Androgens; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D049452:Green Fluorescent Proteins