Interaction between N6-methyladenosine (m6A) modification and noncoding RNAs in cancer

Abstract

As a critical internal RNA modification in higher eukaryotes, N 6-methyladenosine (m 6 A) has become the hotspot of epigenetics research in recent years. Extensive studies on messenger RNAs have revealed that m 6 A affects RNA fate and cell functions in various bioprocesses, such as RNA splicing, export, translation, and stability, some of which seem to be directly or indirectly regulated by noncoding RNAs. Intriguingly, abundant noncoding RNAs such as microRNAs, long noncoding RNAs, circular RNAs, small nuclear RNAs, and ribosomal RNAs are also highly modified with m 6 A and require m 6 A modification for their biogenesis and functions. Here, we discuss the interaction between m 6 A modification and noncoding RNAs by focusing on the functional relevance of m 6 A in cancer progression, metastasis, drug resistance, and immune response. Furthermore, the investigation of m 6 A regulatory proteins and its inhibitors provides new opportunities for early diagnosis and effective treatment of cancer, especially in combination with immunotherapy.

Circular RNA circCUL3 Accelerates the Warburg Effect Progression of Gastric Cancer through Regulating the STAT3/HK2 Axis

“…Evidence has revealed the biogenesis of circRNAs in eukaryocytes, including splicing factor, eukaryotic initiation factor, and N 6 -methyladenosine (m 6 A). 9 , 10 , 11 , 12 , 13 Abundant circRNAs are ubiquitous in eukaryotes, and circRNAs have recently been identified as a new class of regulatory RNAs with genes, including cellular development, neural differentiation, energy metabolism, and occurrence. Being benefited by the covalently closed loop, circRNAs are naturally resistant to exonuclease degradation.…”

Emerging roles of N6-methyladenosine (m6A) modification in breast cancer

“…Several studies have recently shown the importance of the intricate signaling at genetic, transcriptomic, and epigenetic levels that affects tumorigenesis and progression of breast cancer [6][7][8]. N6-Methyladenosine (m 6 A) is one of the most common internal epigenetic modifications found in RNA molecules [9].…”

“…N6-Methyladenosine (m 6 A) is one of the most common internal epigenetic modifications found in RNA molecules [9]. After its discovery by Desrosiers in the 1970s [10], owing to the limitations in technology, research on m 6 A modification has slowly gained attention in the past couple of decades. Recently, with the advances in molecular biology and sequencing, the research on m 6 A modification has made remarkable progress [11][12][13].…”

“…After its discovery by Desrosiers in the 1970s [10], owing to the limitations in technology, research on m 6 A modification has slowly gained attention in the past couple of decades. Recently, with the advances in molecular biology and sequencing, the research on m 6 A modification has made remarkable progress [11][12][13]. To date, m 6 A modifications have been identified in almost every kind of RNA, including mRNA, tRNA, and non-coding RNA, and they are involved in multiple RNA processing and metabolism activities such as splicing, localization, export, translation, stabilization, and decay [14][15][16][17][18].…”

Analysis of N6-methyladenosine (m6A) methyltransferase reveals METTL14 and ZC3H13 as tumor suppressor genes in breast cancer

“…The abnormal expression of m6A "writer" proteins results in abnormal levels of m6A modi cation in tumor cells, which further abnormalizes the metabolism of tumor-related genes mRNA, thereby promoting the development of a variety of cancers [8,9]. The upregulated METTL3 in gastric cancer was positively correlated with the poor prognosis of patients, and METTL3 promoted epithelial-mesenchymal transition of gastric cancer, leading to tumor invasion and metastasis [10].…”