miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer.
BACKGROUND
Prognosis of prostate cancer (PCa) is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line.


METHODS
To determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR).


RESULTS
The in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25) the second was characterized by miR-21 overexpression and RECK underexpression (N = 12), and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16). From men who presented the second profile (miR-21 overexpression and RECK underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025).


CONCLUSIONS
Our results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.
Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil. sasareis@gmail.com
Sabrina Thalita
ST
Reis
José
J
Pontes-Junior
Alberto Azoubel
AA
Antunes
Marcos Francisco
MF
Dall'Oglio
Nelson
N
Dip
Carlo Camargo
CC
Passerotti
Guilherme Ayres
GA
Rossini
Denis Reis
DR
Morais
Adriano Joao
AJ
Nesrallah
Camila
C
Piantino
Miguel
M
Srougi
Katia R
KR
Leite
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D058851:GPI-Linked Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C115460:RECK protein, human; D020780:Matrix Metalloproteinase 9