Expression of the transcribed ultraconserved region 70 and the related long non-coding RNA AC092652.2-202 has prognostic value in Chronic Lymphocytic Leukaemia

Abstract

Chronic lymphocytic leukemia (CLL) development and progression is known to be affected by a plethora of external signals. Among the receptors sensitive to such stimuli, toll-like receptor 9 (TLR9) is of interest because treatment with an agonist like CpG-oligodeoxynucleotide (CpG-ODN) impacts in tumor cell viability and immunogenicity through rendering them more sensitive to T cell-mediated cytotoxicity and chemotherapeutic agents in vitro. Long non-coding RNA (lncRNA) expression alterations have been implicated in various neoplasms including CLL, suggesting that they could also be therapeutic targets and/or clinically useful biomarkers. Transcribed Ultraconserved Regions (T-UCRs) are a class of lncRNA comprising a total of 481 different transcripts with an absolute degree of conservation among human, mouse and rat, that it is suggestive of an essential functional relevance in mammals. In the present study we have explored the possible role of T-UCR in the pathogenesis of CLL performing a global screening using microarrays and qRT-PCR in response to CpG-ODN stimulation. We have identified a AC092652.2-202 as the uc.70-related lncRNA which expression levels are related to the response to CpG-ODN and have prognostic significance in CLL. These findings warrant further studies on the functional characterization of this lncRNA in CLL as well of the particular role of uc.70 sequence in its expression regulation