A substantial number of miRNAs was altered in high fat diet induced prostate cancer growth. - GreenMedInfo Summary
Altered miRNA expression in high-fat diet-induced prostate cancer progression.
Carcinogenesis. 2016 Dec ;37(12):1129-1137. Epub 2016 Oct 7. PMID: 27915273
Recent evidence suggests that a high-fat diet (HFD) plays an important role in prostate carcinogenesis; however, underlying mechanisms largely remain unknown. Here, we investigated microRNA (miRNA) expression changes in murine prostate cancer (PCa) xenografts using two different diets: HFD and control diet. We then assessed the roles and targets of altered miRNAs in HFD-induced PCa progression. We identified 38 up- and 21 downregulated miRNAs in xenografts under HFD conditions using the miRCURY LNA™ microRNA array. The differences in 10 candidate miRNAs were validated using quantitative RT-PCR. We focused on miR-130a because the expression levels were significantly lower in the three PCa cell lines in comparison with benign prostate PINT1B cells. PCa cells cultured in a medium containing HFD mouse serum were associated with significantly higher cell proliferation rates and lower miR-130a expression levels. Further, miR-130a modulated MET expression in PCa cells, and MET was overexpressed in in vitro and in vivo HFD-induced PCa progression models. Moreover, ectopic miR-130a downregulated AR in LNCaP cells and DICER1 in PC-3 and DU145 cells, respectively. In human tissues, as elucidated using laser capture microdissection, the mean miR-130a expression level in cancer epithelium was significantly lower than that in normal epithelium. Furthermore, cytoplasmic MET in PCa tissues wasoverexpressed in patients with higher body mass index. In conclusion, a substantial number of miRNAs was altered in HFD-induced PCa growth. Specifically, miR-130a was attenuated in HFD-induced PCa progression with MET overexpression. miRNAs thus have implications in the mechanism, prevention and treatment of HFD-induced PCa progression.