Identification of a novel lncRNA family that is required for efficient cellular transformation by Bcr-Abl oncogene

ABSTRACT: Aberrantly expressed long noncoding RNAs (lncRNAs) have been described in diverse human diseases and cancer development. Chronic myeloid leukemia (CML) is a hematological malignancy induced by Bcr-Abl hybrid gene. Owing to the development of tyrosine kinase inhibitors (TKIs), especially the first-generation Imatinib, over 90% of CML patients can be cured in recent years. Here we attempt to identify Imatinib-inducible lncRNAs associated with CML by analyzing lncRNA expression profiles in K562 cells after Imatinib or control treatment. LncRNA microarray analysis revealed that numerous lncRNAs were differentially expressed in K562 cells after Imatinib treatment. In this study, we focus on a conserved, Imatinib-inducible lncRNA (IIR) family, named lncRNA-IIRX. Upregulation of lncRNA-IIRX has been detected in both human and mouse Abl-transformed cell lines after Imatinib treatment. Interestingly, lncRNA-IIRX levels were significantly lower in leukemic cells derived from Bcr-Abl-positive ALL patients than those in normal control group. Furthermore, altering lncRNA-IIRX expression remarkably affected survival of Abl-transformed leukemic cells, and tumorigensis induced by these leukemic cells in xenograft mouse model. Knockdown of lncRNA-IIRX in transgenic mice significantly promoted Bcr-Abl-mediated primary bone marrow transformation, and leukemia development in leukemia mouse model. These results indicate that lncRNA-IIRX functions as a suppressor gene in Bcr-Abl-induced tumorigenesis, and may provide novel insights into complicated mechanisms underlying cellular transformation by Bcr-Abl oncogene. This microarray was performed to identify Imatinib-inducible lncRNAs associated with CML.

ORGANISM(S): Homo sapiens

PROVIDER: GSE119770 | GEO | 2019/04/17

REPOSITORIES: GEO