PMID- 23924028
OWN - NLM
STAT- MEDLINE
DCOM- 20141003
LR  - 20211021
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Print)
IS  - 1523-0864 (Linking)
VI  - 20
IP  - 7
DP  - 2014 Mar 1
TI  - miR-205 hinders the malignant interplay between prostate cancer cells and 
      associated fibroblasts.
PG  - 1045-59
LID - 10.1089/ars.2013.5292 [doi]
AB  - AIMS: Tumor microenvironment is a strong determinant for the acquisition of 
      metastatic potential of cancer cells. We have recently demonstrated that 
      cancer-associated fibroblasts (CAFs) elicit a redox-dependent 
      epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, driven by 
      cycloxygenase-2/hypoxia-inducible factor-1 (HIF-1)/nuclear factor-kappaB pathway and 
      enhancing tumor aggressiveness. Here, we investigated the involvement of 
      microRNAs (miRNAs) in tumor-stroma interplay to identify possible tools to 
      counteract oxidative stress and metastasis dissemination. RESULTS: We found that 
      miR-205 is the most downmodulated miRNA in PCa cells upon CAF stimulation, due to 
      direct transcriptional repression by HIF-1, a known redox-sensitive transcription 
      factor. Rescue experiments demonstrated that ectopic miR-205 overexpression in 
      PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell 
      invasion, acquisition of stem cell traits, tumorigenicity, and metastatic 
      dissemination. In addition, miR-205 blocks tumor-driven activation of surrounding 
      fibroblasts by reducing pro-inflammatory cytokine secretion. INNOVATION: Overall, 
      such findings suggest miR-205 as a brake against PCa metastasis by blocking both 
      the afferent and efferent arms of the circuit between tumor cells and associated 
      fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries 
      engaged by reactive stroma. CONCLUSION: The evidence that miR-205 replacement in 
      PCa cells is able not only to prevent but also to revert the 
      oxidative/pro-inflammatory axis leading to EMT induced by CAFs sets the rationale 
      for developing miRNA-based approaches to prevent and treat metastatic disease.
FAU - Gandellini, Paolo
AU  - Gandellini P
AD  - 1 Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei 
      Tumori , Milan, Italy .
FAU - Giannoni, Elisa
AU  - Giannoni E
FAU - Casamichele, Anna
AU  - Casamichele A
FAU - Taddei, Maria Letizia
AU  - Taddei ML
FAU - Callari, Maurizio
AU  - Callari M
FAU - Piovan, Claudia
AU  - Piovan C
FAU - Valdagni, Riccardo
AU  - Valdagni R
FAU - Pierotti, Marco Alessandro
AU  - Pierotti MA
FAU - Zaffaroni, Nadia
AU  - Zaffaroni N
FAU - Chiarugi, Paola
AU  - Chiarugi P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130917
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Cytokines)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (MIRN205 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cytokines/genetics
MH  - Disease Progression
MH  - Down-Regulation/genetics
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Fibroblasts/*pathology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/genetics
MH  - Inflammation/genetics/pathology
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Neoplasm Metastasis/*genetics
MH  - Neoplastic Stem Cells/pathology
MH  - Oxidative Stress/genetics
MH  - Prostatic Neoplasms/*genetics/*pathology
PMC - PMC3929333
EDAT- 2013/08/09 06:00
MHDA- 2014/10/04 06:00
PMCR- 2015/03/01
CRDT- 2013/08/09 06:00
PHST- 2013/08/09 06:00 [entrez]
PHST- 2013/08/09 06:00 [pubmed]
PHST- 2014/10/04 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - 10.1089/ars.2013.5292 [pii]
AID - 10.1089/ars.2013.5292 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2014 Mar 1;20(7):1045-59. doi: 10.1089/ars.2013.5292. Epub 
      2013 Sep 17.