Abstract 4394: Genistein downregulates onco-miR-1260b and inhibits Wnt-signaling in renal cancer cells

Abstract

Abstract Introduction and Objective: Wnt signaling plays an important role in renal cancer and that is modulated by genistein in other cancers. Recently microRNAs have emerged as new regulators of gene expression. Thus we focused on microRNAs to examine the regulatory mechanism of genistein on the Wnt signaling pathway in RCC. Methods: Initially we investigated the effect of genistein on Wnt signaling (TCF reporter assays) in renal cancer cells and using microarray identified candidate miRNAs whose expression was decreased by genistein. We performed functional analyses and investigated the relationship between miRNA expression and renal cancer patient outcomes. We also did 3′UTR luciferase assays to look at direct miRNA regulation of Wnt signaling related genes. Results: Genistein promoted apoptosis while inhibiting RCC cell proliferation and invasion. Genistein also decreased TCF reporter activity in RCC cells. We found that miR-1260b was highly expressed and significantly down-regulated by genistein in RCC cells. The expression of miR-1260b was significantly higher in renal cancer tissues compared to normal and significantly related to over-all shorter survival. Additionally miR-1260b promoted renal cancer cell proliferation and invasion in RCC cells. The 3′UTR luciferase activity of target genes (sFRP1, Dkk2, Smad4) was significantly decreased and their protein expression significantly up-regulated in miR-1260b inhibitor transfected renal cancer cells. Conclusions: Our data suggests that genistein inhibited Wnt signaling by regulating miR-1260b expression in renal cancer cells. Source of Funding: Grants RO1CA138642, RO1CA130860, RO1CA160079, I01BX001123, VA Merit Review and VA Program Project (PI: R. Dahiya). Citation Format: Hiroshi Hirata, Koji Ueno, Yuichiro Tanaka, Z.Laura Tabatabai, Koichi Nakajima, Yuji Hinoda, Nobuhisa Ishii, Rajvir Dahiya. Genistein downregulates onco-miR-1260b and inhibits Wnt-signaling in renal cancer cells. [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 4394. doi:10.1158/1538-7445.AM2014-4394