Abstract 5211: Regulation of SRC kinases by microRNA-3607 located in a frequently deleted locus in prostate cancer

Abstract

Abstract 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 - a microRNA gene located at chr5q14 region- in prostate cancer. Expression analyses of miR-3607 in a clinical cohort of prostate cancer (PCa) specimens showed that miR-3607 is significantly attenuated and low miR-3607 partment of Urology, UCSF School of Mediacinehip and guidance. his guidance. 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. Further, 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. Since 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. Citation Format: Sharanjot Saini, Sumit Arora, Shahana Majid, Varahram Shahryari, Laura Z. Tabatabai, Soichiro Yamamura, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng. Regulation of SRC kinases by microRNA-3607 located in a frequently deleted locus in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5211. doi:10.1158/1538-7445.AM2014-5211