title: Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer.
abstract: OBJECTIVE
  To understand the role of MALAT-1 in prostate cancer we evaluated its expression in prostate cancer tissues and cell lines. We also studied the therapeutic effects of MALAT-1 silencing on castration resistant prostate cancer cells in vitro and in vivo.
  
  
  METHODS
  Quantitative reverse transcriptase-polymerase chain reaction was used to detect MALAT-1 expression in prostate cancer tissues and cell lines. siRNA against MALAT-1 was designed and the silencing effect was examined by quantitative reverse transcriptase-polymerase chain reaction. The biological effects of MALAT-1 siRNA on cells were investigated by examining cell proliferation using a cell counting kit and cell colony assays as well as cell migration by in vitro scratch assay, cell invasion by Transwell® invasion assay and cell cycle by flow cytometry. We further investigated the effect of therapeutic siRNA targeting MALAT-1 on castration resistant prostate cancer in vivo.
  
  
  RESULTS
  MALAT-1 was up-regulated in human prostate cancer tissues and cell lines. Higher MALAT-1 expression correlated with high Gleason score, prostate specific antigen, tumor stage and castration resistant prostate cancer. MALAT-1 down-regulation by siRNA inhibited prostate cancer cell growth, invasion and migration, and induced castration resistant prostate cancer cell cycle arrest in the G0/G1 phases. Importantly, intratumor delivery of therapeutic siRNA targeting MALAT-1 elicited delayed tumor growth and reduced metastasis of prostate cancer xenografts in castrated male nude mice, followed by the concomitant prolongation of survival of tumor bearing mice.
  
  
  CONCLUSIONS
  MALAT-1 may be needed to maintain prostate tumorigenicity and it is involved in prostate cancer progression. Thus, MALAT-1 may serve as a potential therapeutic target for castration resistant prostate cancer.
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Shancheng
authors.initials: S
authors.lastname: Ren
authors.forename: Yawei
authors.initials: Y
authors.lastname: Liu
authors.forename: Weidong
authors.initials: W
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Ji
authors.initials: J
authors.lastname: Lu
authors.forename: Fubo
authors.initials: F
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Jianguo
authors.initials: J
authors.lastname: Hou
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Xu
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: CCK-8; CRPC; Cell Counting Kit-8; LNCaP-AI; LNCaP-androgen independent subtype; M5; M9; MALAT-1; MALAT-1 siRNA-5; MALAT-1 siRNA-9; MALAT1 long non-coding RNA; PBS; PCR; PSA; RNA; RT-PCR; antiandrogens; castration resistant prostate cancer; human; lncRNA; long noncoding RNA; metastasis associated in lung adenocarcinoma transcript 1; phosphate buffered saline; polymerase chain reaction; prostate; prostate specific antigen; prostatic neoplasms; reverse transcriptase-PCR; small interfering