title: miR-195 Inhibits Tumor Progression by Targeting RPS6KB1 in Human Prostate Cancer.
abstract: OBJECTIVE
  To investigate the involvement of hsa-miRNA-195-5p (miR-195) in progression and prognosis of human prostate cancer.
  
  
  METHODS
  qRT-PCR was performed to detect miR-195 expression in both prostate cancer cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene, ribosomal protein S6 kinase, 70 kDa, polypeptide 1 (RPS6KB1) in prostate cancer progression were confirmed on the basis of both in vitro and in vivo systems.
  
  
  RESULTS
  miR-195 downregulation in prostate cancer tissues was significantly associated with high Gleason score (P = 0.001), positive metastasis failure (P < 0.001), and biochemical recurrence (BCR, P < 0.001). Survival analysis identified miR-195 as an independent prognostic factor for BCR-free survival of prostate cancer patients (P = 0.022). Then, we confirmed the tumor suppressive role of miR-195 through prostate cancer cell invasion, migration, and apoptosis assays in vitro, along with tumor xenograft growth, angiogenesis, and invasion in vivo according to both gain-of-function and loss-of-function experiments. In addition, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the reexpression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was closely correlated with aggressive progression and poor prognosis in prostate cancer patients as opposed to miR-195. Furthermore, we identified MMP-9, VEGF, BAD, and E-cadherin as the downstream effectors of miR-195-RPS6KB1 axis.
  
  
  CONCLUSIONS
  The newly identified miR-195-RPS6KB1 axis partially illustrates the molecular mechanism of prostate cancer progression and represents a novel potential therapeutic target for prostate cancer treatment.
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, and Guangdong Key Laboratory of Urology, Guangzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cai
authors.affiliation: Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, China.
authors.forename: Qing-Biao
authors.initials: QB
authors.lastname: Chen
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Zhao-Dong
authors.initials: ZD
authors.lastname: Han
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, and Guangdong Key Laboratory of Urology, Guangzhou, China. Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Hui-Chan
authors.initials: HC
authors.lastname: He
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Chen
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Sheng-Bang
authors.initials: SB
authors.lastname: Yang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Yong-Ding
authors.initials: YD
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, China. Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Zeng
authors.affiliation: Central Hospital of Panyu District, Guangzhou, China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Qin
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Liang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Qi-Shan
authors.initials: QS
authors.lastname: Dai
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Fu-Neng
authors.initials: FN
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Shu-lin
authors.initials: SL
authors.lastname: Wu
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, and Guangdong Key Laboratory of Urology, Guangzhou, China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Zeng
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, and Guangdong Key Laboratory of Urology, Guangzhou, China. Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, China. Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China. zhongwd2009@live.cn cwu2@partners.org.
authors.forename: Wei-De
authors.initials: WD
authors.lastname: Zhong
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Department of Urology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. zhongwd2009@live.cn cwu2@partners.org.
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000737:chemistry / Q000235:genetics*; D047368:Tumor Burden / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051025:bcl-Associated Death Protein; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D020780:Matrix Metalloproteinase 9