MicroRNA-3162-5p-mediated crosstalk between Kallikrein family members including prostate-specific antigen in prostate cancer

Australian Prostate Cancer BioResource, Farhana Mating, Varinder Jeet, Srilakshmi Srinivasan, Alexandre S. Cristino, Janaththani Panchadsaram, Judith A. Clements, Jyotsna Batra*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)771-780
Number of pages10
JournalClinical Chemistry
Volume65
Issue number6
DOIs
Publication statusPublished - Jun 2019
Externally publishedYes

Cite this

Australian Prostate Cancer BioResource, Mating, F., Jeet, V., Srinivasan, S., Cristino, A. S., Panchadsaram, J., ... Batra, J. (2019). MicroRNA-3162-5p-mediated crosstalk between Kallikrein family members including prostate-specific antigen in prostate cancer. Clinical Chemistry, 65(6), 771-780. https://doi.org/10.1373/clinchem.2018.295824