Abstract 5340: MicroRNA-720 promotes cell proliferation and invasion in prostate cancer cells

MicroRNAs (miRNAs) are highly conserved, single stranded, non-coding RNAs of approximately 21 - 24 nucleotides that regulate gene expression by posttranscriptional silencing of specific target RNAs, by repressing translation or cleaving RNA transcripts by binding to the 3’ untranslated region (3’UTR) of the target messenger RNAs. miRNAs regulate diverse cellular processes such as cell-cycle progression, proliferation, apoptosis and development. miRNAs also have been shown to function as oncogenes or tumor suppressor genes. MicroRNA profiling has shown that miR-720 was up-regulated in cancer tissues, however the function of miR-720 in cancer has not been studied. Here we studied the functional effects of miR-720 on prostate cancer cells. We found that miR-720 was up-regulated in human prostate cancer tissues compared to adjacent normal tissues. We also found that miR-720 was up-regulated in prostate PC-3 cancer cell line compared with normal prostate cell line, RWPE1 cells. Transfection of miR-720 into prostate cancer cells, PC-3 and DU145 cells, decreased apoptosis, promoted cell proliferation and cell invasion. Transfection of anti-miR-720 into PC-3 cells increased apoptosis, inhibited cell proliferation and cell invasion. These results indicated that miR-720 has oncogenic functions in prostate cancer cells. In-silico analysis suggests that miR-720 targets genes of DR1, a down-regulator of global transdcription, and SWI5, a component of a complex required for double-strand break repair, which have tumor suppressive functions. Luciferase assays indicated that miR-720 binds to the 3’ UTR of these genes in prostate cancer cells, suggesting that these genes are targets of miR-720. Our results suggest that miR-720 promotes malignancy by targeting DR1 and SWI5 in prostate cancer cells. Funding: National Institutes of Health through Grant Number RO1CA138642, RO1CA130860 and RO1CA160079 and VA Merit Review and VA Program Project. Citation Format: Soichiro Yamamura, Takeshi Chiyomaru, Shinichiro Fukuhara, Sharanjot Saini, Shahana Majid, Guoren Deng, Vary Shahryary, Sumit Arora, Inik Chang, Yuichiro Tanaka, Peter Carroll, Rajvir Dahiya. MicroRNA-720 promotes cell proliferation and invasion in prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5340. doi:10.1158/1538-7445.AM2013-5340