MOLECULAR INVESTIGATION OF LONG NON-CODING RNA EXPRESSION IN PATIENTS WITH SENSITIVE AND RESISTANT CHRONIC MYELOID LEUKEMIA
Project no. 17 · Status: Kapanmış · 2016
Summary
Long non-coding RNAs (lncRNAs) are non-coding RNAs that are > 200nt, and many have been found to be involved in many epigenetic mechanisms such as chromatin modification, genomic imprinting, and regulation of gene expression. Deregulated expression of Nuclear paraspeckle assembly transcript 1 (NEAT1) has been found to be related with the progression of several cancers. The expression of NEAT1 normally results in the production of a class of nuclear RNA-protein complex named ‘paraspeckles’ in mammalian nucleus. The function of NEAT1 and ‘paraspeckles’ in the BCR-ABL associated pathways (AKT, ERK, STAT pathways) in KML still remains largely unknown, but recent studies showed NEAT1 overexpression in leukemia cell line reduced MDR (multi drug resistance) induced pathways in KML. In this study we aimed to investigate the role of lncRNA NEAT1 in BCR-ABL mediated tumorigenesis in CML. We hypothesize that NEAT1 might target imatinib resistance-associated genes and downstream of the BCR-ABL fusion protein genes (PI3K / Akt, mTOR, JAK-STAT) in CML. For this reason, our study may contribute to an elucidation of imatinib response and imatinib resistance mechanisms in association with NEAT1 and ‘paraspeckles’ in CML.Furthermore, since BCR/ABL was found to translocate from the cytoplasm to the nucleus following genotoxic stress, and then associates with ATR-dependent DNA damage response pathways, which is also found to be regulated by ‘paraspeckles’ and NEAT1 expression, it becomes intriguing to test if NEAT1 might be a novel target for the treatment of chronic myeloid leukemia. Key words: Chronic myeloid leukemia, long non-coding RNAs, resistance mechanism of tyrosine kinase inhibitor in CML