Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer.

Journal Article (Journal Article)

PURPOSE: 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. MATERIALS AND 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.

Full Text

Duke Authors

Cited Authors

  • Ren, S; Liu, Y; Xu, W; Sun, Y; Lu, J; Wang, F; Wei, M; Shen, J; Hou, J; Gao, X; Xu, C; Huang, J; Zhao, Y; Sun, Y

Published Date

  • December 2013

Published In

Volume / Issue

  • 190 / 6

Start / End Page

  • 2278 - 2287

PubMed ID

  • 23845456

Electronic International Standard Serial Number (EISSN)

  • 1527-3792

Digital Object Identifier (DOI)

  • 10.1016/j.juro.2013.07.001

Language

  • eng

Conference Location

  • United States