Abstract PR10: HiClinc-1, a highly conserved Cancer-Testis lncRNA, regulates cell proliferation and tumor onset

Long non-coding RNA (lncRNAs) have been shown to play an important role is a variety of cellular processes including cancer initiation and progression. Recently, we described a landscape of lncRNA using RNA-Seq data from more than 5000 cancer samples from 18 tissue types. Using novel bioinformatics based approach we were able to discover almost 50,000 novel transcripts. This list includes a subset of lncRNAs that contain ultra-conserved elements (UCE) termed “Highly Conserved Long Intergenic Non-Coding RNAs (HICLINCs)”. This provides a new opportunity for exploring the functions of highly conserved lncRNAs using genomic approaches. Among them, we focus on an lncRNA which we have termed HiClinc-1 (Highly Conserved Intergenic long-noncoding RNA-1), that is specifically expressed only in testis in benign tissue, and re-expressed in a broad range of cancer types. We described that HiClinc-1 exists in the messenger Ribonucleoprotein (mRNP) complex and binds to Insulin-Like Growth Factor 2 mRNA Binding Protein 1 (IGF2BP1), one of the component of mRNP complex in both human and zebrafish. HiClinc-1 regulates cell proliferation both in vivo and in vitro through the regulation of IGF2BP1's downstream target Insulin-Like Growth Factor 2 (IGF2). HiClinc-1 also enhanced tumor growth in mouse xenograft model. Notably, Human-HiClinc-1 injection in zebrafish embryos accelerated the onset and growth of NRAS K61-induced melanoma. Similarly, HiClinc-1 knockout background showed delayed onset of NRAS K61-induced melanoma. Taken together, we identified a novel Cancer-Testis lncRNA, which is highly conserved through human to zebrafish that can be a potential therapeutic target for cancer treatment. Citation Format: Yasuyuki Hosono, John Prensner, Matthew Iyer, Yashar Niknafs, Rohit Malik, Anton Poliakov, Xuhong Cao, Jordan Shavit, Rohit Mehra, Weibin Zhou, Arul M. Chinnaiyan. HiClinc-1, a highly conserved Cancer-Testis lncRNA, regulates cell proliferation and tumor onset. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr PR10.