miR-618: possible control over TIMP-1 and its expression in localized prostate cancer

Author(s)

Ivanovic, Renato F. ^[1] ; Viana, Nayara I. ^[1] ; Morais, Denis R. ^[1] ; Moura, Caio ^[1] ; Silva, Iran A. ^[1] ; Leite, Katia R. ^[1] ; Pontes-Junior, Jose ^[1] ; Nahas, William C. ^{[2, 3]} ; Srougi, Miguel ^[1] ; Reis, Sabrina T. ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Urol, Lab Med Invest LIM55, Sch Med, Ave Dr Arnaldo 455, 2nd Floor, Room 2145, BR-01246903 Sao Paulo - Brazil

^[2] ICESP, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Urol, Urooncol Grp, Sch Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: BMC CANCER; v. 18, OCT 19 2018.
• Web of Science Citations: 1

Abstract

BackgroundThe imbalance between the action of the tissue inhibitors of matrix metalloproteinases (TIMPs) and the matrix metalloproteinases (MMPs) is one component of metastasis physiology. TIMP-1 overrides MMP-9 activity in cancer and might be regulated by miR-618. The aims of this study were to clarify whether TIMP-1 expression is modified by miR-618 and to clarify the effect of miR-618 expression on the invasion of prostate cancer cells. We also studied miR-618 expression in surgical specimens of patients with localized prostate cancer submitted to open radical prostatectomy.MethodsAfter transfection of miR-618 or its antagonist in DU145 cells, qRT-PCR for TIMP-1/MMP-9 and both ELISA and zymography for MMP-9 were performed. Total miRNA was extracted from surgical specimens of PCa, and miR-618 expression was examined for correlations with Gleason score, pathological status and biochemical recurrence.ResultsDU145 cells transfected with miR-618 had a 76% reduction in TIMP-1 expression relative to control cells (p=0.003). miR-618 inhibition reduced MMP-9 expression by 31% (p=0.032) and MMP-9 absorbance evaluated with ELISA assay (p=0.06).Zymography suggested higher MMP-9 activity in DU145 cells transfected with miR-618 than those transfected with miR-618 inhibitor, but the difference was not significant (p=0.55). However, miR-618 expression was lower in surgical specimens of patients with Gleason score>7 (p=0.08) and more advanced disease (p=0.07).ConclusionsIn vitro, miR-618 overexpression decreases TIMP-1 and miR-618 inhibition decreases MMP-9, suggesting that miR-618 might be an oncomiR. However, the analysis of clinical samples of localized prostate cancer revealed an inconsistent pattern, as increased miR-618 expression was associated with lower Gleason score and pathological status. Further studies are needed to address whether miR-618 is a context-dependent miRNA. (AU)

• FAPESP's process: 15/00845-6 - Analysis of the miRNAs involved in the regulation of MMP2 and MMP9 and regulators, and the implication of this adjustment in cell invasion in prostate adenocarcinoma process: in vivo and in vitro studies
• Grantee: Renato Fidelis Ivanovic
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 12/21833-8 - Analysis of miRNAs involved in regulation of MMP2 and MMP9 and its implication of this regulators and regulating the process of cell migration and invasion of the prostate adenocarcinoma
• Grantee: Sabrina Thalita dos Reis Faria
• Support Opportunities: Regular Research Grants