The Regulatory Function of ADAR1-mediated RNA Editing in Hematological Malignancies
RNA editing,an essential post-transcriptional reaction occurring in double-stranded RNA(dsRNA),generates informational diversity in the transcriptome and proteome.In mammals,the main type of RNA editing is the conversion of adenosine to inosine(A-to-I),processed by adenosine deaminases acting on the RNAs(ADARs)family,and interpreted as guanosine during nucleotide base-pairing.It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events,catalyzed by the primarily responsible enzyme,ADAR1.In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma,dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions,non-coding regions,and immature miRNA precursors.Subsequently,aberrant A-to-I editing states result in altered molecular events,such as protein-coding sequence changes,intron retention,alternative splicing,and miRNA biogenesis inhibition.As a vital factor of the generation and stemness maintenance in leukemia stem cells(LSCs),disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation,apoptosis inhibition and drug resistance.At present,novel drugs designed to target RNA editing(e.g.,rebecsinib)are under development and have achieved outstanding results in animal experiments.Compared with traditional antitumor drugs,epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies,and provide new treatment options for patients.This review summarized the recent advances in the regulation mechanism of ADAR 1-mediated RNA editing events in hematologic malignancies,and further discussed the medical potential and clinical application of ADAR1.
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