OBJECTIVE: Patients die of prostate cancer (CaP) because predictably after a period of response to androgen withdrawal, their CaP becomes castrate resistant. In this paper, we discuss the role that microRNAs (miRNAs) may play in this process. METHODS: miRNAs are a group of endogenous, small non-coding RNA molecules that are thought to be responsible for the regulation of up to 30% of gene expression. The miRNA expression profile between androgen responsive and castrate resistant CaP cell lines is compared. Functional studies were carried out to identify the importance of the miRNA targets in controlling this process. RESULTS: There were 17 differentially expressed miRNAs found, 10 up-regulated and 7 down-regulated. Among these, miRNA-125b was found to have the ability of rendering LNCaP cells resistant to androgen withdrawal. It was found to be androgen regulated and one of its targets, BAK1, was identified as being involved in how these CaP cells undergo apoptosis functionally. CONCLUSION: miRNA-125b, at least in the CaP cell lines tested, is involved in the development of castrate resistance. While clearly this miRNA is only part of the answer, miRNAs may lead us in a new direction in trying to solve the central problem in CaP.
OBJECTIVE:Patients die of prostate cancer (CaP) because predictably after a period of response to androgen withdrawal, their CaP becomes castrate resistant. In this paper, we discuss the role that microRNAs (miRNAs) may play in this process. METHODS: miRNAs are a group of endogenous, small non-coding RNA molecules that are thought to be responsible for the regulation of up to 30% of gene expression. The miRNA expression profile between androgen responsive and castrate resistant CaP cell lines is compared. Functional studies were carried out to identify the importance of the miRNA targets in controlling this process. RESULTS: There were 17 differentially expressed miRNAs found, 10 up-regulated and 7 down-regulated. Among these, miRNA-125b was found to have the ability of rendering LNCaP cells resistant to androgen withdrawal. It was found to be androgen regulated and one of its targets, BAK1, was identified as being involved in how these CaP cells undergo apoptosis functionally. CONCLUSION:miRNA-125b, at least in the CaP cell lines tested, is involved in the development of castrate resistance. While clearly this miRNA is only part of the answer, miRNAs may lead us in a new direction in trying to solve the central problem in CaP.
Authors: P Mathijs Voorhoeve; Carlos le Sage; Mariette Schrier; Ad J M Gillis; Hans Stoop; Remco Nagel; Ying-Poi Liu; Josyanne van Duijse; Jarno Drost; Alexander Griekspoor; Eitan Zlotorynski; Norikazu Yabuta; Gabriella De Vita; Hiroshi Nojima; Leendert H J Looijenga; Reuven Agami Journal: Cell Date: 2006-03-24 Impact factor: 41.582
Authors: Lee P Lim; Nelson C Lau; Philip Garrett-Engele; Andrew Grimson; Janell M Schelter; John Castle; David P Bartel; Peter S Linsley; Jason M Johnson Journal: Nature Date: 2005-01-30 Impact factor: 49.962
Authors: George Adrian Calin; Cinzia Sevignani; Calin Dan Dumitru; Terry Hyslop; Evan Noch; Sai Yendamuri; Masayoshi Shimizu; Sashi Rattan; Florencia Bullrich; Massimo Negrini; Carlo M Croce Journal: Proc Natl Acad Sci U S A Date: 2004-02-18 Impact factor: 11.205
Authors: Lorenzo F Sempere; Mette Christensen; Asli Silahtaroglu; Mads Bak; Catherine V Heath; Gary Schwartz; Wendy Wells; Sakari Kauppinen; Charles N Cole Journal: Cancer Res Date: 2007-12-15 Impact factor: 12.701
Authors: Shuangli Mi; Jun Lu; Miao Sun; Zejuan Li; Hao Zhang; Mary Beth Neilly; Yungui Wang; Zhijian Qian; Jie Jin; Yanming Zhang; Stefan K Bohlander; Michelle M Le Beau; Richard A Larson; Todd R Golub; Janet D Rowley; Jianjun Chen Journal: Proc Natl Acad Sci U S A Date: 2007-12-04 Impact factor: 11.205
Authors: Hamed R Goodarzi; Ali Abbasi; Mojtaba Saffari; Mohammad B Tabei; Mohammad R Noori Daloii Journal: Mol Biol Rep Date: 2009-10-10 Impact factor: 2.316
Authors: A Kroiss; S Vincent; M Decaussin-Petrucci; E Meugnier; J Viallet; A Ruffion; F Chalmel; J Samarut; N Allioli Journal: Oncogene Date: 2014-07-28 Impact factor: 9.867