Abstract 1826: A critical role of LincRNA-Up6 in Bcr-Abl-induced tumorigenesis.

Abstract Long noncoding RNAs (lncRNAs) have been implicated in numerous human malignancies, including leukemia. Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) is a stem cell disease induced by Bcr-Abl hybrid gene. In an attempt to provide better understanding of the mechanisms by which Bcr-Abl mediates cellular transformation, lncRNA microarray was used to determine the differentially expressed non protein-coding genes in K562 human leukemic cells in response to disruption of Bcr-Abl expression. All the lncRNA genes whose expressions were altered by at least 2-fold were clustered and displayed. We further investigated the functional involvement of selected lncRNA genes in regulating cell proliferation, cell survival and tumor formation. Interestingly, expression of a long intergenic noncoding RNA which we named as lincRNA-Up6 was found to be greatly up-regulated by silencing the Bcr-Abl expression in K562 cells. We showed that forced over-expression of lincRNA-Up6 sensitized imatinib-induced apoptosis in Bcr-Abl transformed cells. In addition, we observed that over-expression of lincRNA-Up6 significantly inhibited K562 xenograft growth in nude mice. Furthermore, we found that lincRNA-Up6 was involved in negative regulation of STAT5-dependent expression of anti-apoptotic Bcl-XL protein. Importantly, our experiments showed that expression of lincRNA-Up6 had profound effects on signaling pathways associated with development of leukemia stem cells of CML, resulting in inhibition of Bcr-Abl-mediated tumor formation. Together, these results suggest that lincRNA-Up6 suppresses Bcr-Abl-induced tumorigenesis, and the tumor suppressor function of lincRNA-Up6 may be of significance for the development of novel therapeutic strategies for treating CML. Citation Format: Jilong Chen, Guijie Guo, Qingzheng Kang. A critical role of LincRNA-Up6 in Bcr-Abl-induced tumorigenesis. [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 1826. doi:10.1158/1538-7445.AM2013-1826 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.