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Título: miR-618: possible control over TIMP-1 and its expression in localized prostate cancer
Autor: IVANOVIC, Renato F.VIANA, Nayara I.MORAIS, Denis R.MOURA, CaioSILVA, Iran A.LEITE, Katia R.PONTES-JUNIOR, JoseNAHAS, William C.SROUGI, MiguelREIS, Sabrina T.
Citación: BMC CANCER, v.18, article ID 992, 6p, 2018
Resumen: 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.
Aparece en las colecciones:

Artigos e Materiais de Revistas Científicas - FM/MCG
Departamento de Cirurgia - FM/MCG

Artigos e Materiais de Revistas Científicas - HC/ICESP
Instituto do Câncer do Estado de São Paulo - HC/ICESP

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - LIM/55
LIM/55 - Laboratório de Urologia

Artigos e Materiais de Revistas Científicas - ODS/03
ODS/03 - Saúde e bem-estar


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