| First Author | Latonen L | Year | 2017 |
| Journal | Am J Pathol | Volume | 187 |
| Issue | 11 | Pages | 2546-2557 |
| PubMed ID | 28827140 | Mgi Jnum | J:248760 |
| Mgi Id | MGI:6094651 | Doi | 10.1016/j.ajpath.2017.07.012 |
| Citation | Latonen L, et al. (2017) In Vivo Expression of miR-32 Induces Proliferation in Prostate Epithelium. Am J Pathol 187(11):2546-2557 |
| abstractText | 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. |
