Tampere University of Technology

TUTCRIS Research Portal

In Vivo Expression of miR-32 Induces Proliferation in Prostate Epithelium

Research output: Contribution to journalArticleScientificpeer-review


Original languageEnglish
Pages (from-to)2546-2557
Number of pages12
JournalAmerican Journal of Pathology
Issue number11
Publication statusPublished - 1 Nov 2017
Publication typeA1 Journal article-refereed


miRNAs are important regulators of gene expression and are often deregulated in cancer. We have previously shown that miR-32 is an androgen receptor–regulated miRNA overexpressed in castration-resistant prostate cancer and that miR-32 can improve prostate cancer cell growth in vitro. To assess the effects of miR-32 in vivo, we developed transgenic mice overexpressing miR-32 in the prostate. The study indicated that transgenic miR-32 expression increases replicative activity in the prostate epithelium. We further observed an aging-associated increase in the incidence of goblet cell metaplasia in the prostate epithelium. Furthermore, aged miR-32 transgenic mice exhibited metaplasia-associated prostatic intraepithelial neoplasia at a low frequency. When crossbred with mice lacking the other allele of tumor-suppressor Pten (miR-32xPten+/− mice), miR-32 expression increased both the incidence and the replicative activity of prostatic intraepithelial neoplasia lesions in the dorsal prostate. The miR-32xPten+/− mice also demonstrated increased goblet cell metaplasia compared with Pten+/− mice. By performing a microarray analysis of mouse prostate tissue to screen downstream targets and effectors of miR-32, we identified RAC2 as a potential, and clinically relevant, target of miR-32. We also demonstrate down-regulation of several interesting, potentially prostate cancer–relevant genes (Spink1, Spink5, and Casp1) by miR-32 in the prostate tissue. The results demonstrate that miR-32 increases proliferation and promotes metaplastic transformation in mouse prostate epithelium, which may promote neoplastic alterations in the prostate.

ASJC Scopus subject areas

Publication forum classification

Field of science, Statistics Finland