Abstract 46: Functional analysis of long noncoding RNAs in Bcr-Abl-mediated tumorigenesis

Abstract

Abstract Human genome is pervasively transcribed and the majority does not have apparent protein coding potential, which is defined as noncoding RNA (ncRNA). Long noncoding RNAs (lncRNAs) are greater than 200 nucleotides in length, transcribed by RNA polymerase II or III, and poorly conserved. Aberrant expression of numerous functional lncRNAs is associated with various human cancers. Chronic myeloid leukemia (CML) is a hematologic malignancy associated with a translocation between chromosome 9 and 22 that results in the formation of bcr-abl hybrid gene which occurs in over 90% of CML cases. However, the role of lncRNAs in Bcr-Abl-mediated chronic myeloid leukemia (CML) is not fully understood. In this study, we performed a comprehensive analysis of lncRNAs in human CML cells using a microarray of cDNAs encoding lncRNAs. The microarray analysis revealed 338 upregulated lncRNAs and 108 downregulated lncRNAs after silencing Bcr-Abl in human CML cells. To identify functional lncRNAs that are important in Bcr-Abl-mediated transformation, we selected the most significantly affected lncRNAs for further studies. These lncRNAs were examined by ORF finder from NCBI and protein-coding potential was determined. We identified several lncRNAs that acted as a key regulator of Bcr-Abl-mediated cellular transformation. Expression of these lncRNAs was further examined in response to disruption of Bcr-Abl expression or by inhibiting Bcr-Abl kinase activity in K562 cells and leukemic cells derived from CML patients. Experiments including ectopic overexpression or knockdown of these lncRNAs were performed to address the role and mechanism of how these lncRNAs function in the leukemic cells. Together, these results reveal that several lncRNAs are critically involved in Bcr-Abl-mediated cellular transformation and suggest a potential strategy for the treatment of Bcr-Abl-positive leukemia. Note: This abstract was not presented at the conference. Citation Format: Guijie Guo, Xuefei Wang, Jilong Chen. Functional analysis of long noncoding RNAs in Bcr-Abl-mediated tumorigenesis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 46.