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

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. Quantitative reverse transcriptase-polymerase c...

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Vydané v:The Journal of urology Ročník 190; číslo 6; s. 2278
Hlavní autori: Ren, Shancheng, Liu, Yawei, Xu, Weidong, Sun, Yi, Lu, Ji, Wang, Fubo, Wei, Min, Shen, Jian, Hou, Jianguo, Gao, Xu, Xu, Chuanliang, Huang, Jiaoti, Zhao, Yi, Sun, Yinghao
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.12.2013
Predmet:
Animals
Cell Cycle - genetics
Humans
Male
Mice
Prostatic Neoplasms, Castration-Resistant - drug therapy
Prostatic Neoplasms, Castration-Resistant - genetics
Prostatic Neoplasms, Castration-Resistant - metabolism
RNA, Long Noncoding - biosynthesis
RNA, Long Noncoding - genetics
Tumor Cells, Cultured
lncRNA
RNA
MALAT-1 siRNA-5
castration resistant prostate cancer
M5
MALAT-1 siRNA-9
M9
reverse transcriptase-PCR
LNCaP-AI
RT-PCR
long noncoding RNA
CCK-8
small interfering
LNCaP-androgen independent subtype
human
polymerase chain reaction
PSA
PBS
MALAT1 long non-coding RNA
prostate specific antigen
Cell Counting Kit-8
phosphate buffered saline
MALAT-1
prostatic neoplasms
prostate
antiandrogens
metastasis associated in lung adenocarcinoma transcript 1
CRPC
PCR
ISSN:1527-3792, 1527-3792
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Shrnutí: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. 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. 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. 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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1527-3792
1527-3792
DOI:10.1016/j.juro.2013.07.001