Abstract 992: Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Abstract

Abstract Increasing evidence suggests that lncRNAs play critical roles in a diverse set of biological processes, including proliferation, differentiation, embryogenesis, neurogenesis and stem cell pluripotency. It has been reported that many lncRNAs regulate gene expression and various post-transcriptional processes, including splicing, transport, translation and degradation of mRNA. Furthermore, recent studies have shown that Many lncRNAs play critical roles in tumor development and progression. We attempted to identify lncRNAs critical for the tumorigenicity of colon tumor cells. We have found that a lncRNA termed UPAT is required for the survival and tumorigenicity of colorectal cancer cells. We also show that UPAT interacts with and stabilizes the epigenetic factor UHRF1 by interfering with its β-TrCP-mediated ubiquitination. UHRF1 plays key roles in multiple biological processes, including proliferation and development. Moreover, UHRF1 is overexpressed in various tumors, including colon cancer, and plays a critical role in the proliferation and survival of tumor cells. Furthermore, we demonstrate that UHRF1-UPAT complex upregulate SCD1 and SPRY4, which play critical roles in the survival and proliferation of colon cancer cells. Our findings suggest that UPAT-mediated stabilization of UHRF1 is critical for the proliferation and tumorigenicity of colon tumor cells. Our results suggest that UHRF1-UPAT axis may be a promising molecular target for colon cancer therapies. Citation Format: Kenzui Taniue, Yasuko Takeda, Tetsu Akiyama. Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 992.