MicroRNA-3162-5p-Mediated Crosstalk between Kallikrein Family Members Including Prostate-Specific Antigen in Prostate Cancer.
Clin Chem
; 65(6): 771-780, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-31018918
ABSTRACT
BACKGROUND:
MicroRNAs mediate biological processes through preferential binding to the 3' untranslated region (3' UTR) of target genes. Studies have shown their association with prostate cancer (PCa) risk through single-nucleotide polymorphisms (SNPs), known as miRSNPs. In a European cohort, 22 PCa risk-associated miRSNPs have been identified. The most significant miRSNP in the 3' UTR of Kallikrein-related peptidase 3 (KLK3) created a binding site for miR-3162-5p. Here we investigated the miR-3162-5p-KLK interaction and the clinical implication of miR-3162-5p in PCa.METHODS:
We tested the role of miR-3162-5p in PCa etiology using IncuCyte live-cell imaging and anchorage-independent growth assays. The effect of miR-3162-5p on KLK and androgen receptor (AR) expression was measured by RT-quantitative (q)PCR and target pulldown assays. KLK3 proteolytic activity was determined by DELFIA® immunoassay. Mass spectrometry identified pathways affected by miR-3162-5p. miR-3162-5p expression was measured in clinical samples using RT-qPCR.RESULTS:
miR-3162-5p affected proliferation, migration, and colony formation of LNCaP cells by regulating the expression of KLK2-4 and AR by direct targeting. KLK3 protein expression was regulated by miR-3162-5p consistent with lower KLK3 proteolytic activity observed in LNCaP-conditioned media. KLK/AR pulldown and mass spectrometry analysis showed a potential role of miR-3162-5p in metabolic pathways via KLK/AR and additional targets. Increased miR-3162-5p expression was observed in prostate tumor tissues with higher Gleason grade.CONCLUSIONS:
Our study provides an insight into possible involvement of miR-3162-5p in PCa etiology by targeting KLKs and AR. It highlights clinical utility of miR-3162-5p and its interactive axis as a new class of biomarkers and therapeutic targets for PCa.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Calicreínas
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Antígeno Prostático Específico
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MicroARNs
Tipo de estudio:
Prognostic_studies
Límite:
Humans
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Male
Idioma:
En
Revista:
Clin Chem
Asunto de la revista:
QUIMICA CLINICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Australia