Research advances of N6‐methyladenosine in diagnosis and therapy of pancreatic cancer

Abstract

Background N6‐methyladenosine (m6A) is the addition of a methyl group on the N6 position of adenosine and is the most prevalent and abundant epigenetic modification in eukaryote mRNA. m6A marks are added to mRNA by the m6A methyltransferase complex (“writers”), removed by m6A demethylases (“erasers”), and recognized by m6A‐binding proteins (“readers”). Recent evidence has shown that the m6A modification plays a crucial role in the pathogenic mechanism and malignant progression of pancreatic cancer, with roles in cell survival, proliferation, migration, invasion, tumor metastasis, and drug resistance. Methods Literature was searched in Pubmed and Web of Science for the following keywords: “N6‐methyladenosine”, “pancreatic cancer”, “epigenetic modification”, “immunotherapy”. Results Among classical m6A regulators, while METTL3, METTL14, WTAP, FTO, YTHDF2, IGF2BP1–3, hnRNPC, and NKAP are upregulated in pancreatic cancer, METTL16 and ALKBH5 are downregulated in pancreatic cancer. m6A modification has been investigated in pancreatic cancer therapy. Conclusion Dysregulated m6A and its related factors in pancreatic cancer cells and patients indicate their potential values as novel biomarkers in pancreatic cancer diagnosis and targeted therapy.

M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma

“…In recent decades, increasing research has suggested that m6A modification and lncRNA play pivotal roles in areas such as immunity, inflammation and, most importantly, tumor biology [ 40 , 41 , 42 , 43 , 44 ] However, current efforts in this regard have only concentrated on single lncRNA or m6A regulator proteins [ 45 , 46 ]. Combinational studies based on integrated m6A and lncRNA have not been widely carried out.…”

“…In recent years, m6A has become a hot topic in tumor biology [ 58 , 59 ]. Generally speaking, current research on m6A in PDAC is still at an early stage [ 45 , 46 ]. Nevertheless, emerging evidence has revealed that m6A regulator proteins are involved in the carcinogenesis, progression and therapy resistance of PDAC [ 32 , 33 , 34 , 35 , 36 , 46 ].…”

Emerging role of RNA modification and long noncoding RNA interaction in cancer

“…Abnormal m6A modification of lncRNA is currently found in PC tissues and cell lines (Fig. 3) [137,138]. Chen et al found that METTL14-modified LncRNA LIFR-AS1 promotes the progression of PC.…”

N6-methyladenosine (m6A) reader IGF2BP1 facilitates clear-cell renal cell carcinoma aerobic glycolysis

“…N 6 -methyladenosine (m 6 A) modification is firstly described in 1971 years, which has shown critical roles in mRNA metabolism and become focus recently ( Chen et al, 2022 ; Li et al, 2022 ). Methyltransferase installed the m 6 A modification on mRNA, including methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and the Wilms tumor 1-associated protein (WTAP) ( Lin et al, 2022 ; Luo et al, 2022 ).…”