miR-21: an oncomir on strike in prostate cancer

Molecular Cancer

Research

Valentina Profumo¹  Rosanna Supino¹  Paolo Gandellini¹  Maurizio Callari¹  Nicole Longoni¹  Maria Grazia Daidone¹  Nadia Zaffaroni¹  Marco Folini¹  Marzia Pennati¹  Silvia Veneroni¹  Maurizio Colecchia²  Roberto Salvioni³  Riccardo Valdagni⁴ 

[1] Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133, Milan, Italy;Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133, Milan, Italy;Department of Urology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133, Milan, Italy;Prostate Program, Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133, Milan, Italy;

关键词: Radical Prostatectomy;    DU145 Cell;    Locked Nucleic Acid;    Passenger Strand;    Pdcd4 Protein;   

DOI  :  10.1186/1476-4598-9-12

 received in 2009-08-26, accepted in 2010-01-21,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAberrant expression of microRNAs, small non-coding RNA molecules that post-transcriptionally repress gene expression, seems to be causatively linked to the pathogenesis of cancer. In this context, miR-21 was found to be overexpressed in different human cancers (e.g. glioblastoma, breast cancer). In addition, it is thought to be endowed with oncogenic properties due to its ability to negatively modulate the expression of tumor-suppressor genes (e.g. PTEN) and to cause the reversion of malignant phenotype when knocked- down in several tumor models. On the basis of these findings, miR-21 has been proposed as a widely exploitable cancer-related target. However, scanty information is available concerning the relevance of miR-21 for prostate cancer. In the present study, we investigated the role of miR-21 and its potential as a therapeutic target in two prostate cancer cell lines, characterized by different miR-21 expression levels and PTEN gene status.ResultsWe provide evidence that miR-21 knockdown in prostate cancer cells is not sufficient per se i) to affect the proliferative and invasive potential or the chemo- and radiosensitivity profiles or ii) to modulate the expression of the tumor-suppressors PTEN and Pdcd4, which in other tumor types were found to be regulated by miR-21. We also show that miR-21 is not differently expressed in carcinomas and matched normal tissues obtained from 36 untreated prostate cancer patients subjected to radical prostatectomy.ConclusionsOverall, our data suggest that miR-21 is not a central player in the onset of prostate cancer and that its single hitting is not a valuable therapeutic strategy in the disease. This supports the notion that the oncogenic properties of miR-21 could be cell and tissue dependent and that the potential role of a given miRNA as a therapeutic target should be contextualized with respect to the disease.

【 授权许可】

Unknown   
© Folini et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.