Public Health & Health Science Division, ULAB

RNA modifications including adenosine-to-inosine (A-to-I) editing and N6-methyladenosine (m6A) play important roles in post-transcriptional gene regulation and havebeen identified as major factors in the initiation and spread of cancer. The most prevalent internal alteration in eukaryotic mRNA, m6A, is dynamically controlled by "writers"(METTL3/METTL14), "erasers" (FTO/ALKBH5), and "readers" (YTH domain proteins), whichcollectively affect RNA stability, splicing, translation, and destruction. Studies have shown that dysregulation of m6A plays a role in cancers such leukemia, breast cancer, and clear cell renal cell carcinoma through pathways involving METTL3 and SETD2 mutations. This dysregulation has been closely linked to tumor growth, metastasis, and therapeutic resistance. Similar to this,A-to-I RNA editing, which is mostly mediated by ADAR1, modifies RNA transcripts withoutaltering DNA sequences and promotes protein variety and immune control. By modifyingendogenous double-stranded RNA, blocking immune identification by sensors like MDA5 and PKR, and facilitating immune evasion in interferon-rich environments, ADAR1 enhances tumor survival in cancer. Through changed transcripts like AZIN1 and GLI1, overexpression of ADAR1 has also been connected to the development of tumors. These results collectively show that A-to-I RNA editing and m6A alteration are both attractive therapeutic targets for precision cancer therapy approaches in addition to being biomarkers of disease progression.