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

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author IVANOVIC, Renato F. FMUSP-HC
VIANA, Nayara I. FMUSP-HC
MORAIS, Denis R. FMUSP-HC
MOURA, Caio FMUSP-HC
SILVA, Iran A. FMUSP-HC
LEITE, Katia R. FMUSP-HC
PONTES-JUNIOR, Jose FMUSP-HC
NAHAS, William C. FMUSP-HC
SROUGI, Miguel FMUSP-HC
REIS, Sabrina T. FMUSP-HC
dc.date.issued 2018
dc.identifier.citation BMC CANCER, v.18, article ID 992, 6p, 2018
dc.identifier.issn 1471-2407
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/29323
dc.description.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.
dc.description.sponsorship · Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2015/00845-6, 2012/21833-8]
dc.language.iso eng
dc.publisher BMC
dc.relation.ispartof BMC Cancer
dc.rights openAccess
dc.subject Prostate cancer; MMP-9; TIMP-1; microRNA; Invasion
dc.subject.other matrix metalloproteinases; messenger-rna; biomarkers; inhibitors; tissue; prognosis
dc.title miR-618: possible control over TIMP-1 and its expression in localized prostate cancer
dc.type article
dc.rights.holder Copyright BMC
dc.description.group LIM/55
dc.identifier.doi 10.1186/s12885-018-4930-4
dc.identifier.pmid 30340564
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author IVANOVIC, Renato F.:FM:
hcfmusp.author VIANA, Nayara I.:HC:ICHC
hcfmusp.author MORAIS, Denis R.:HC:ICHC
hcfmusp.author MOURA, Caio:FM:
hcfmusp.author SILVA, Iran A.:HC:ICHC
hcfmusp.author LEITE, Katia R.:FM:MCG
hcfmusp.author PONTES-JUNIOR, Jose:HC:ICHC
hcfmusp.author NAHAS, William C.:FM:MCG
hcfmusp.author SROUGI, Miguel:FM:MCG
hcfmusp.author REIS, Sabrina T.:FM:
hcfmusp.origem.id WOS:000447737100007
hcfmusp.origem.id 2-s2.0-85055077806
hcfmusp.publisher.city LONDON
hcfmusp.publisher.country ENGLAND
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dc.description.index MEDLINE
hcfmusp.citation.scopus 1
hcfmusp.citation.wos 1


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