Novel insights on m6A RNA methylation in tumorigenesis: a double-edged sword

Abstract

N6-methyladenosine (m6A), the most prevalent modification of mammalian RNA, has received increasing attention. Although m6A has been shown to be associated with biological activities, such as spermatogenesis modulation, cell spermatogenesis and pluripotency, Drosophila sex determination, and the control of T cell homeostasis and response to heat shock, little is known about its roles in cancer biology and cancer stem cells. Recent articles have noted that some genes have abnormal m6A expression after tumorigenesis, including genes ABS2, RARA, MYB, MYC, ADAM19 and FOX1. Abnormal changes in the m6A levels of these genes are closely related to tumour occurrence and development. In this review, we summarized the ‘dual edge weapon’ role of RNA methylation in the tumorigenesis. We discussed RNA methylation could lead to not only tumour progression but also tumour suppression. Moreover, we clarified that the abnormal changes in the m6A enrichment of specific loci contribute to tumour occurrence and development, thereby representing a novel anti-cancer strategy by restoration to balanced RNA methylation in tumour cells.

Transcriptome-wide map of m6A circRNAs identified in hypoxic pulmonary hypertension rat model

“…m 6 A abundance was significantly reduced in PASMCs and PAECs when exposed to hypoxia (0.107% ± 0.007 vs. 0.054% ± 0.118, p = 0.023 in PASMCs; 0.114% ± 0.011 vs. 0.059% ± 0.008, p = 0.031 in PAECs, Fig 6A). m 6 A abundance in circRNAs was lower than it in mRNAs (0.1–0.4%) (17, 18). Next, we confirmed the back-splicing of circXpo6 and circTmtc3 by CIRI software.…”

“…We suggest that circRNAs can be used as biomarkers because it is differentially enriched in specific cell types or tissues and not easily degraded (6). Also, the aberrant m 6 A methylation may contribute to tumor formation and m 6 A RNAs may be a potential therapy target for tumor (17). Therefore, we suppose that m 6 A circRNAs may also be used as a potential diagnostic marker or therapy target in HPH in the future.…”

“…N 6 -methyladenosine (m 6 A) is regarded as one part of “epitranscriptomics’’ and identified as the most universal modification on mRNAs and noncoding RNAs (ncRNAs) in eukaryotes (13, 14). DRm 6 ACH (D denotes A, U or G; R denotes A, G; H denotes A, C, or U) is a consensus motif occurred in m 6 A modified RNAs (15–17). m 6 A modification is mainly enriched around the stop codons, at 3’untranslated regions (3’ UTRs) and within internal long exons (17–19).…”

“…DRm 6 ACH (D denotes A, U or G; R denotes A, G; H denotes A, C, or U) is a consensus motif occurred in m 6 A modified RNAs (15–17). m 6 A modification is mainly enriched around the stop codons, at 3’untranslated regions (3’ UTRs) and within internal long exons (17–19). Several catalyzed molecules act as “writers”, “readers”, and “erasers” to regulate the m 6 A modification status (14).…”

“…Several catalyzed molecules act as “writers”, “readers”, and “erasers” to regulate the m 6 A modification status (14). The methyltransferase complex is known as writers, including methyltransferase-like-3, −14 and −16 (METTL3/METTL14/METTL16), Wilms tumour 1-associated protein (WTAP), RNA binding motif protein 15 (RBM15), vir like m 6 A methyltransferase associated (KIAA1429) and zinc finger CCCH-type containing 13 (ZC3H13), appending m 6 A on DRACH (17, 20, 21). METTL3 is regarded as the core catalytically active subunit, while METTL14 and WTAP play a structural role in METTL3’s catalytic activity (18, 22).…”