title: miR-21: an oncomir on strike in prostate cancer.
abstract: BACKGROUND
  Aberrant 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Overall, 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.
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, Milan, 20133, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Folini
authors.forename: Paolo
authors.initials: P
authors.lastname: Gandellini
authors.forename: Nicole
authors.initials: N
authors.lastname: Longoni
authors.forename: Valentina
authors.initials: V
authors.lastname: Profumo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Callari
authors.forename: Marzia
authors.initials: M
authors.lastname: Pennati
authors.forename: Maurizio
authors.initials: M
authors.lastname: Colecchia
authors.forename: Rosanna
authors.initials: R
authors.lastname: Supino
authors.forename: Silvia
authors.initials: S
authors.lastname: Veneroni
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvioni
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdagni
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011836:Radiation Tolerance / Q000187:drug effects / Q000528:radiation effects
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017239:Paclitaxel; D002945:Cisplatin