METTL16 regulates m6A methylation on chronic hepatitis B associated gene HLA-DPB1 involved in liver fibrosis

Abstract

The role of genetic factors in the occurrence and progression of CHB (CHB) is still not fully explored. In recent years, genome-wide association studies on CHB patients have demonstrated that a large number of CHB-associated single nucleotide polymorphisms exist in the gene intron, which may regulate expression at the transcriptional level. Modification of RNA m6A methylation is one of the key mechanisms regulating gene expression. Here we show that METTL16, an m6A regulator involved in mRNA intron splicing, is differentially expressed in CHB the tissue of patients who has definite diagnosis of mild and severe fibrosis. At the same time, there are also significant differences in the expression of CHB-associated genes such as HLA-DPA1 and HLA-DPB1. The expression of HLA-DPB1 is related to METTL16. Furthermore, analyses of RNA binding of METTL16 and HLA-DPB1 show that the silencing of METTL16 in astrocytes downregulates m6A and expression of HLA-DPB1. In conclusion, METTL16 participates in the progression of CHB fibrosis by regulating the m6A level and expression of HLA-DPB1.

m6A RNA methylation drives kidney fibrosis by upregulating β-catenin signaling

“…In this regard, recent studies show that METTL14 is increased in DKD, and knockdown of METTL14 protects against streptozotocin-induced kidney fibrosis in mice 50 . Furthermore, WTAP and METTL16 have been shown to participate in regulating cardiac fibrosis and chronic hepatitis B fibrosis, respectively 51 , 52 . Future studies on the role of these methyltransferases in kidney fibrogenesis are warranted.…”

Changes in m6A in Steatotic Liver Disease

“…The expression of METTL16 was significantly higher in livers from chronic hepatitis B patients with severe fibrosis compared to those with only mild fibrosis and METTL16 was positively correlated the expression of genes associated with chronic hepatitis B (CHB), including HLA-DPB1 and HLA-DPA1 [154].…”

RNA methylations in hepatic fibrosis, a gradually emerging new treatment strategy

“…Furthermore, silencing METTL16 suppressed the expression of m6A and HLA-DPB1. This suggests that METTL16 may be a new target for the diagnosis and treatment of CHB fibrosis [ 107 ].…”