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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP-
dc.contributor.authorIVANOVIC, Renato F.-
dc.contributor.authorVIANA, Nayara I.-
dc.contributor.authorMORAIS, Denis R.-
dc.contributor.authorMOURA, Caio-
dc.contributor.authorSILVA, Iran A.-
dc.contributor.authorLEITE, Katia R.-
dc.contributor.authorPONTES-JUNIOR, Jose-
dc.contributor.authorNAHAS, William C.-
dc.contributor.authorSROUGI, Miguel-
dc.contributor.authorREIS, Sabrina T.-
dc.identifier.citationBMC CANCER, v.18, article ID 992, 6p, 2018-
dc.description.abstractBackgroundThe 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.-
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo [2015/00845-6, 2012/21833-8]-
dc.relation.ispartofBMC Cancer-
dc.subjectProstate cancer-
dc.subject.othermatrix metalloproteinases-
dc.titlemiR-618: possible control over TIMP-1 and its expression in localized prostate cancer-
dc.rights.holderCopyright BMC-
dc.type.categoryoriginal article-
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Appears in Collections:

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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