Non-Mutational Changes of Autophagy Marker LC3A in Patients with Acute Myeloid Leukemia; Effect of DNA Methylation and Expression Level of LncRNA-GAS5 and miRNA-155-5p, A Case Control Study

Abstract

Clinical translation of autophagy modulators is tied to thoroughly acquainted with the precise state of this process and its regulators in a particular cancer. LC3Av1 is a marker of autophagosome membrane that has been contributed with pathobiology of myriad of human cancers. In the present study, we examined the effect of promoter methylation and miR-155 and LncRNA-GAS5 (GAS5) expression levels on transcription of LC3Av1 in AML patients. The study included 60 patients with de novo AML and 20 subjects with normal bone marrow cellular composition. Methylation-Sensitive high resolution melting (MS-HRM) was performed for analysis of LC3Av1 CpG island methylation and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for assessing LC3Av1, GAS5 and miR-155 expression levels. There was a significant elevation in the expression level of miR-155 and repression of LC3Av1 in AML samples. We found that LC3Av1 downregulation was negatively associated with its CpG island hypermethylation and miR-155 expression. Aging leads to overexpression of LC3Av1. GAS5 neither was differently expressed in AML patients compared to control samples nor has been related to LC3Av1 expression. The present study revealed that epigenetic changes like DNA methylation and alteration of miR-155 have a pivotal role in repression of autophagy marker LC3Av1, which potentially could provide the important clues of prognostic and therapeutic targets. The optimal strategies for clinical implementation of autophagy in AML is yet to be fully achieved and deserve further studies.