Long Noncoding RNA MALAT-1 is a New Potential Therapeutic Target for Castration Resistant Prostate Cancer

被引：319

作者：

Ren, Shancheng ^{[1
]}

Liu, Yawei ^{[2
]}

Xu, Weidong ^{[1
]}

Sun, Yi ^{[1
]}

Lu, Ji ^{[1
]}

Wang, Fubo ^{[1
]}

Wei, Min ^{[1
]}

Shen, Jian ^{[1
]}

Hou, Jianguo ^{[1
]}

Gao, Xu ^{[1
]}

Xu, Chuanliang ^{[1
]}

Huang, Jiaoti ^{[4
]}

Zhao, Yi ^{[3
]}

Sun, Yinghao ^{[1
]}

机构：

[1] Second Mil Med Univ, Shanghai Changhai Hosp, Dept Urol, Shanghai, Peoples R China

[2] Chinese Peoples Liberat Army, Gen Staff Dept, Hlth Div, Guard Bur, Beijing, Peoples R China

[3] Chinese Acad Sci, Adv Comp Res Ctr, Inst Comp Technol, Key Lab Intelligent Informat Proc,Bioinformat Res, Beijing, Peoples R China

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

来源：

JOURNAL OF UROLOGY | 2013年 / 190卷 / 06期

基金：

中国国家自然科学基金;

关键词：

prostate; prostatic neoplasms; MALAT1 long non-coding RNA; human; RNA; small interfering; antiandrogens; IN-VITRO; METASTASIS; CARCINOMAS; THERAPIES; SURVIVAL; BIOLOGY; CELLS; GENE;

D O I：

10.1016/j.juro.2013.07.001

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

100201 [内科学]; 100221 [泌尿外科学];

摘要：

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 (R) 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.

引用

页码：2278 / 2287

页数：10

共 29 条

[1]

Noncoding RNA in development [J].

Amaral, Paulo P. ;

Mattick, John S. .

MAMMALIAN GENOME, 2008, 19 (7-8) :454-492

[2]

Bussemakers MJG, 1999, CANCER RES, V59, P5975

[3]

Ultraconserved regions encoding ncRNAs are, altered in human leukemias and carcinomas [J].

Calin, George A. ;

Liu, Chang-Gong ;

Ferracin, Manuela ;

Hyslop, Terry ;

Spizzo, Riccardo ;

Sevignani, Cinzia ;

Fabbri, Muller ;

Cimmino, Amelia ;

Lee, Eun Joo ;

Wojcik, Sylwia E. ;

Shimizu, Masayoshi ;

Tili, Esmerina ;

Rossi, Simona ;

Taccioli, Cristian ;

Pichiorri, Flavia ;

Liu, Xiuping ;

Zupo, Simona ;

Herlea, Vlad ;

Gramantieri, Laura ;

Lanza, Giovanni ;

Alder, Hansjuerg ;

Rassenti, Laura ;

Volinia, Stefano ;

Schmittgen, Thomas D. ;

Kipps, Thomas J. ;

Negrini, Massimo ;

Croce, Carlo M. .

CANCER CELL, 2007, 12 (03) :215-229

[4]

The transcriptional landscape of the mammalian genome [J].

Carninci, P ;

Kasukawa, T ;

Katayama, S ;

Gough, J ;

Frith, MC ;

Maeda, N ;

Oyama, R ;

Ravasi, T ;

Lenhard, B ;

Wells, C ;

Kodzius, R ;

Shimokawa, K ;

Bajic, VB ;

Brenner, SE ;

Batalov, S ;

Forrest, ARR ;

Zavolan, M ;

Davis, MJ ;

Wilming, LG ;

Aidinis, V ;

Allen, JE ;

Ambesi-Impiombato, X ;

Apweiler, R ;

Aturaliya, RN ;

Bailey, TL ;

Bansal, M ;

Baxter, L ;

Beisel, KW ;

Bersano, T ;

Bono, H ;

Chalk, AM ;

Chiu, KP ;

Choudhary, V ;

Christoffels, A ;

Clutterbuck, DR ;

Crowe, ML ;

Dalla, E ;

Dalrymple, BP ;

de Bono, B ;

Della Gatta, G ;

di Bernardo, D ;

Down, T ;

Engstrom, P ;

Fagiolini, M ;

Faulkner, G ;

Fletcher, CF ;

Fukushima, T ;

Furuno, M ;

Futaki, S ;

Gariboldi, M .

SCIENCE, 2005, 309 (5740) :1559-1563

[5]

Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution [J].

Cheng, J ;

Kapranov, P ;

Drenkow, J ;

Dike, S ;

Brubaker, S ;

Patel, S ;

Long, J ;

Stern, D ;

Tammana, H ;

Helt, G ;

Sementchenko, V ;

Piccolboni, A ;

Bekiranov, S ;

Bailey, DK ;

Ganesh, M ;

Ghosh, S ;

Bell, I ;

Gerhard, DS ;

Gingeras, TR .

SCIENCE, 2005, 308 (5725) :1149-1154

[6]

Landmarks in non-hormonal pharmacological therapies for castration-resistant prostate cancer [J].

Clarke, Noel W. .

BJU INTERNATIONAL, 2012, 110 :14-29

[7]

Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation [J].

Dinger, Marcel E. ;

Amaral, Paulo P. ;

Mercer, Tim R. ;

Pang, Ken C. ;

Bruce, Stephen J. ;

Gardiner, Brooke B. ;

Askarian-Amiri, Marjan E. ;

Ru, Kelin ;

Solda, Giulia ;

Simons, Cas ;

Sunkin, Susan M. ;

Crowe, Mark L. ;

Grimmond, Sean M. ;

Perkins, Andrew C. ;

Mattick, John S. .

GENOME RESEARCH, 2008, 18 (09) :1433-1445

[8]

Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1 [J].

Fu, XQ ;

Ravindranath, L ;

Tran, N ;

Petrovics, G ;

Srivastava, S .

DNA AND CELL BIOLOGY, 2006, 25 (03) :135-141

[9]

The functional role of long non-coding RNA in human carcinomas [J].

Gibb, Ewan A. ;

Brown, Carolyn J. ;

Lam, Wan L. .

MOLECULAR CANCER, 2011, 10

[10]

Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis [J].

Gupta, Rajnish A. ;

Shah, Nilay ;

Wang, Kevin C. ;

Kim, Jeewon ;

Horlings, Hugo M. ;

Wong, David J. ;

Tsai, Miao-Chih ;

Hung, Tiffany ;

Argani, Pedram ;

Rinn, John L. ;

Wang, Yulei ;

Brzoska, Pius ;

Kong, Benjamin ;

Li, Rui ;

West, Robert B. ;

van de Vijver, Marc J. ;

Sukumar, Saraswati ;

Chang, Howard Y. .

NATURE, 2010, 464 (7291) :1071-U148

← 1 2 3 →