title: MicroRNA-30d promotes angiogenesis and tumor growth via MYPT1/c-JUN/VEGFA pathway and predicts aggressive outcome in prostate cancer.
abstract: Even though aberrant expression of microRNA (miR)-30d has been reported in prostate cancer (PCa), its associations with cancer progression remain contradictory. The aim of this study was to investigate clinical significance, biological functions and underlying mechanisms of miR-30d deregulation in PCa.
  
  
  
  Involvement of miR-30d deregulation in malignant phenotypes of PCa was demonstrated by clinical sample evaluation, and in vitro and in vivo experiments. The mechanisms underlying its regulatory effect on tumor angiogenesis were determined.
  
  
  
  miR-30d over-expression was observed in both PCa cells and clinical specimens. High-miR-30d was distinctly associated with high pre-operative PSA and Gleason score, advanced clinical and pathological stages, positive metastasis and biochemical recurrence (BCR), and reduced overall survival of PCa patients. Through gain- and loss-of-function experiments, we found that miR-30d promoted PCa cell proliferation, migration, invasion, and capillary tube formation of endothelial cells, as well as in vivo tumor growth and angiogenesis in a mouse model. Simulation of myosin phosphatase targeting subunit 1 (MYPT1), acting as a direct target of miR-30d, antagonized the effects induced by miR-30d up-regulation in PCa cells. Notably, miR-30d/MYPT1 combination was identified as an independent factor to predict BCR of PCa patients. Furthermore, miR-30d exerted its pro-angiogenesis function, at least in part, by inhibiting MYPT1, which in turn, increased phosphorylation levels of c-JUN and activated VEGFA-induced signaling cascade in endothelial cells.
  
  
  
  miR-30d and/or its target gene MYPT1 may serve as novel prognostic markers of PCa. miR-30d promotes tumor angiogenesis of PCa through MYPT1/c-JUN/VEGFA pathway.
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.|Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, China.
authors.forename: Zhuo-Yuan
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.|Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.|Department of Urology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, 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, 510180, 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, 510180, China.|Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.|Department of Urology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: Jian-Heng
authors.initials: JH
authors.lastname: Ye
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.|Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Ying-Ke
authors.initials: YK
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, 510180, China.|Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Ru-Jun
authors.initials: RJ
authors.lastname: Mo
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.|Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Lu
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.|Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yang-Jia
authors.initials: YJ
authors.lastname: Zhuo
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, China.|Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
authors.forename: Fu-Neng
authors.initials: FN
authors.lastname: Jiang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
authors.forename: Zhao-Dong
authors.initials: ZD
authors.lastname: Han
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.|Department of Urology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Wu
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China. zhongwd2009@live.cn.|Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. zhongwd2009@live.cn.|Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510230, China. zhongwd2009@live.cn.|Graduate school of Jinan University, Guangzhou, 510632, China. zhongwd2009@live.cn.
authors.forename: Wei-de
authors.initials: WD
authors.lastname: Zhong
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China. cwu2@mgh.harvard.edu.|Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. cwu2@mgh.harvard.edu.|Department of Urology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. cwu2@mgh.harvard.edu.
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D043263:Myosin-Light-Chain Phosphatase / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun; D042461:Vascular Endothelial Growth Factor A; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human
keywords: MicroRNA-30d; Myosin phosphatase targeting subunit 1; Prognosis; Prostate cancer; Tumor angiogenesis