Epigenetic modifications in acute myeloid leukemia: The emerging role of circular RNAs (Review).

Canonical epigenetic modifications, which include histone modification, chromatin remodeling and DNA methylation, play key roles in numerous cellular processes. Epigenetics underlies how cells that posses DNA with similar sequences develop into different cell types with different functions in an organism. Earlier epigenetic research has primarily been focused at the chromatin level. However, the number of studies on epigenetic modifications of RNA, such as N1‑methyladenosine, 2'‑O‑ribosemethylation, inosine, 5‑methylcytidine, N6‑methyladenosine (m6A) and pseudouridine, has seen an increase. Circular RNAs (circRNAs), a type of RNA species that lacks a 5' cap or 3' poly(A) tail, are abundantly expressed in acute myeloid leukemia (AML) and may regulate disease progression. circRNAs possess various functions, including microRNA sponging, gene transcription regulation and RNA‑binding protein interaction. Furthermore, circRNAs are m6A methylated in other types of cancer, such as colorectal and hypopharyngeal squamous cell cancers. Therefore, the critical roles of circRNA epigenetic modifications, particularly m6A, and their possible involvement in AML are discussed in the present review. Epigenetic modification of circRNAs may become a diagnostic and therapeutic target for AML in the future.