miR-193b is an epigenetically regulated putative tumor suppressor in prostate cancer

被引:111
作者
Rauhala, Hanna E. [1 ,2 ]
Jalava, Sanni E. [1 ,2 ]
Isotalo, Jarkko [1 ,2 ]
Bracken, Hazel [1 ,2 ]
Lehmusvaara, Saara [1 ,2 ]
Tammela, Teuvo L. J. [2 ,3 ]
Oja, Hannu [4 ]
Visakorpi, Tapio [1 ,2 ]
机构
[1] Univ Tampere, Inst Med Technol, FIN-33014 Tampere, Finland
[2] Tampere Univ Hosp, Tampere, Finland
[3] Univ Tampere, Dept Urol, FIN-33014 Tampere, Finland
[4] Univ Tampere, Tampere Sch Publ Hlth, FIN-33014 Tampere, Finland
基金
芬兰科学院;
关键词
prostatic carcinoma; neoplasia; CpG; methylation; miRNA; DOWN-REGULATION; BREAST-CANCER; MICRORNA; EXPRESSION; CELLS; CARCINOGENESIS; IDENTIFICATION; METHYLATION; PROGRESSION; SIGNATURE;
D O I
10.1002/ijc.25162
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
miRNAs have proven to be key regulators of gene expression and are differentially expressed in various diseases, including cancer. Our aim was to identify epigenetically dysregulated genes in prostate cancer. We performed miRNA expression profiling after relieving epigenetic modifications in 6 prostate cancer cell lines and nonmalignant prostate epithelial cells. Thirty-eight miRNAs showed increased expression in any prostate cancer cell line after 5-aza-2 '-deoxycytidine (5azadC) and trichostatin A (TSA) treatments. Six of these also had decreased expression in clinical prostate cancer samples compared to benign prostatic hyperplasia. Among these, miR-193b was methylated in 22Rv1 cell line at a CpG island similar to 1 kb upstream of the miRNA locus. Expressing miR-193b in 22Rv1 cells using pre-miR-193b oligonucleotides caused a significant growth reduction (p < 0.001) resulting from a decrease of cells in S-phase of the cell cycle (p < 0.01). In addition, the anchorage independent growth was partially inhibited in transiently miR-193b-expressing 22Rv1 cells (p < 0.01). Altogether, our data suggest that miR-193b is an epigenetically silenced putative tumor suppressor in prostate cancer.
引用
收藏
页码:1363 / 1372
页数:10
相关论文
共 27 条
[1]   Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J].
Calin, GA ;
Sevignani, C ;
Dan Dumitru, C ;
Hyslop, T ;
Noch, E ;
Yendamuri, S ;
Shimizu, M ;
Rattan, S ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2999-3004
[2]   A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia [J].
Calin, GA ;
Ferracin, M ;
Cimmino, A ;
Di Leva, G ;
Shimizu, M ;
Wojcik, SE ;
Iorio, MV ;
Visone, R ;
Sever, NI ;
Fabbri, M ;
Iuliano, R ;
Palumbo, T ;
Pichiorri, F ;
Roldo, C ;
Garzon, R ;
Sevignani, C ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (17) :1793-1801
[3]   MicroRNA biogenesis: there's more than one way to skin a cat [J].
Faller, Michael ;
Guo, Feng .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2008, 1779 (11) :663-667
[4]   Identification of patterns in biological sequences at the ALGGEN server:: PROMO and MALGEN [J].
Farré, D ;
Roset, R ;
Huerta, M ;
Adsuara, JE ;
Roselló, L ;
Albà, MM ;
Messeguer, X .
NUCLEIC ACIDS RESEARCH, 2003, 31 (13) :3651-3653
[5]   Amplification of the urokinase gene and the sensitivity of prostate cancer cells to urokinase inhibitors [J].
Helenius, MA ;
Savinainen, KJ ;
Bova, GS ;
Visakorpi, T .
BJU INTERNATIONAL, 2006, 97 (02) :404-409
[6]   Genome-Wide Profiling of Histone H3 Lysine 4 and Lysine 27 Trimethylation Reveals an Epigenetic Signature in Prostate Carcinogenesis [J].
Ke, Xi-Song ;
Qu, Yi ;
Rostad, Kari ;
Li, Wen-Cheng ;
Lin, Biaoyang ;
Halvorsen, Ole Johan ;
Haukaas, Svein A. ;
Jonassen, Inge ;
Petersen, Kjell ;
Goldfinger, Naomi ;
Rotter, Varda ;
Akslen, Lars A. ;
Oyan, Anne M. ;
Kalland, Karl-Henning .
PLOS ONE, 2009, 4 (03)
[7]   hTERT-immortalized prostate epithelial and stromal-derived cells:: an authentic in vitro model for differentiation and carcinogenesis [J].
Kogan, I ;
Goldfinger, N ;
Milyavsky, M ;
Cohen, M ;
Shats, I ;
Dobler, G ;
Klocker, H ;
Wasylyk, B ;
Voller, M ;
Aalders, T ;
Schalken, JA ;
Oren, M ;
Rotter, V .
CANCER RESEARCH, 2006, 66 (07) :3531-3540
[8]   RAPID FLOW CYTOFLUOROMETRIC ANALYSIS OF MAMMALIAN-CELL CYCLE BY PROPIDIUM IODIDE STAINING [J].
KRISHAN, A .
JOURNAL OF CELL BIOLOGY, 1975, 66 (01) :188-193
[9]   Expression of urokinase-type plasminogen activator system in prostate cancer: Correlation with clinicopathological outcomes in patients undergoing radical prostatectomy [J].
Kumano, Masafumi ;
Miyake, Hideaki ;
Muramaki, Mototsugu ;
Furukawa, Junya ;
Takenaka, Atsushi ;
Fujisawa, Masato .
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, 2009, 27 (02) :180-186
[10]   Identification of novel genes coding for small expressed RNAs [J].
Lagos-Quintana, M ;
Rauhut, R ;
Lendeckel, W ;
Tuschl, T .
SCIENCE, 2001, 294 (5543) :853-858