miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer

Abstract

BackgroundPrognosis 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.Materials and methodsTo 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).ResultsThe 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).ConclusionsOur 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.

Circulating microRNAs as novel prognosis biomarkers for head and neck squamous cell carcinoma

“…MiR-21 is known as an oncomiR, which is over-expressed miRNA in many cancers, and functions to regulate cell proliferation and apoptosis during neoplastic progression in a variety of cancers. 8,9 The decrement of miR-21 and miR-223 after surgery was concordant with previous report in HNSCC.…”

miRNAs as novel biomarkers in the management of prostate cancer

“…Another invasionrelated gene regulated by miR-21 is RECK, a matrix metalloproteinase inhibitor. Neutralizing miR-21 represses the matrix metalloproteinase levels and reverses the invasive phenotype [62]. Recently, Wang et al [63] found that miR-573 expression was significantly lower in metastatic tissues than matched primary PCa.…”

Pericellular proteolysis in cancer

“…Potential miRNA-binding sites have been predicted in the 39 untranslated region of ADAM17, uPA, and several MMPs (Dalmay and Edwards 2006;Bracken et al 2014), and a growing number of studies have provided functional validation of miRNAmediated regulation of proteases in cancer . It has also been reported that miRNAs contribute to the down-regulation of inhibitors and other protease regulators, which in turn leads to protease activation (Gabriely et al 2008;Reis et al 2012). In future studies, it will be critical to determine whether the other reported mechanisms that alter protease expression in cancer similarly change protein localization and consequently impact pericellular proteolysis.…”