Regulation of SRC Kinases by microRNA-3607 Located in a Frequently Deleted Locus in Prostate Cancer

Genomic studies suggest that deletions at chromosome (chr) 5q region (particularly chr5q14-q23) are frequent in prostate cancer, implicating this region in prostate carcinogenesis. However, the genes within this region are largely unknown. Here, we report for the first time the widespread attenuation of miR-3607, an miRNA gene located at chr5q14 region, in prostate cancer. Expression analyses of miR-3607 in a clinical cohort of prostate cancer specimens showed that miR-3607 is significantly attenuated and low miR-3607 expression is correlated with tumor progression and poor survival outcome in prostate cancer. Our analyses suggest that miR-3607 expression may be a clinically significant parameter with an associated diagnostic potential. We examined the functional significance of miR-3607 in prostate cancer cell lines and found that miR-3607 overexpression led to significantly decreased proliferation, apoptosis induction, and decreased invasiveness. Furthermore, our results suggest that miR-3607 directly represses oncogenic SRC family kinases LYN and SRC in prostate cancer. In view of our results, we propose that miR-3607 plays a tumor-suppressive role in prostate cancer by regulating SRC kinases that in turn regulates prostate carcinogenesis. To our knowledge, this is the first report that: (i) identifies a novel role for miR-3607 located in a frequently deleted region of prostate cancer and (ii) defines novel miRNA-mediated regulation of SRC kinases in prostate cancer. Because SRC kinases play a central role in prostate cancer progression and metastasis and are attractive targets, this study has potential implications in the design of better therapeutic modalities for prostate cancer management. (C) 2014 AACR.