Roles of m6A modification in regulating PPER pathway in cadmium-induced pancreatic ß cell death.

Cadmium can lead to the death of pancreatic ß cells, thus affecting the synthesis and secretion of insulin. However, the specific mechanisms underlying the cadmium-induced pancreatic ß cell death have not been fully understood. In this study, roles of m6A modification in regulating protein processing in endoplasmic reticulum (PPER) pathway in cadmium-induced pancreatic ß cell death were explored. Our results demonstrated that cell viability and RNA m6A modification level were decreased, while apoptosis rates increased after CdSO4 treatment in pancreatic ß cells (NIT-1). In addition, expressions of Bcl-2, Xbp1, Col3a1, Bax, Chop, Dnajb1, and Hsp90aa1 were all significantly changed in CdSO4 treatment cells. The m6A agonist entacapone (Ent) can prominently reverse the cytotoxicity effects of CdSO4 and alleviate the changes of protein expression induced by CdSO4 treatment. By contrast, m6A inhibitor 3-Deazaadenosine (DAA) can synergistically enhance the cytotoxicity of CdSO4 and aggravate the disorder of protein levels caused by CdSO4 treatment. Interestingly, the results of the immunoprecipitation experiment indicate that Ythdc2, one of m6A binding proteins, may regulate the PPER pathway molecules in an m6A-dependent manner. In summary, our findings provide new directions for the prevention and treatment of the impairment of pancreatic ß cell function induced by cadmium.

Emerging roles of epigenetics in lead-induced neurotoxicity.

Lead is a common environmental heavy metal contaminant. Humans are highly susceptible to lead accumulation in the body, which causes nervous system damage and leads to a variety of nervous system diseases, such as Alzheimer's disease, Parkinson's disease, and autism spectrum disorder. Recent research has focused on the mechanisms of lead-induced neurotoxicity at multiple levels, including DNA methylation, histone modifications, and non-coding RNAs, which are involved in various lead-induced nervous system diseases. We reviewed the latest articles and summarised the emerging roles of DNA methylation, histone modification, and non-coding RNAs in lead-induced neurotoxicity. Our summary provides a theoretical basis and directions for future research on the prevention, diagnosis, and treatment of lead-induced neurological diseases.

Novel insights into mutual regulation between N6-methyladenosine modification and LncRNAs in tumors.

N6-methyladenosine (m6A), one of the most common RNA methylation modifications, has emerged in recent years as a new layer of the regulatory mechanism controlling gene expression in eukaryotes. As a reversible epigenetic modification, m6A not only occurs on mRNAs but also on Long non-coding RNAs (LncRNAs). As we all known, despite LncRNAs cannot encode proteins, they affect the expression of proteins by interacting with mRNAs or miRNAs, thus playing important roles in the occurrence and development of a variety of tumors. Up to now, it has been widely accepted that m6A modification on LncRNAs affects the fate of the corresponding LncRNAs. Interestingly, levels and functions of m6A modifications are also mediated by LncRNAs through affecting the m6A methyltransferases (METTL3, METTL14, WTAP, METTL16, etc.), demethylases (FTO, ALKBH5) and methyl-binding proteins (YTHDFs, YTHDCs, IGF2BPs, HNRNPs, etc.), which are collectively referred to as "m6A regulators". In this review, we summarized the mutual regulation mechanisms between N6-methyladenosine modification and LncRNAs in cancer progression, metastasis, invasion and drug resistance. In detail, we focus on the specific mechanisms of m6A modification, which is mediated by methyltransferases and demethylases, involves in the regulation of LncRNA levels and functions in the first part. And section two intensively displays the mediation roles of LncRNAs in m6A modification via changing the regulatory proteins. At last part, we described the interaction effects between LncRNAs and methyl-binding proteins of m6A modification during various tumor occurrence and development.

Emerging Mutual Regulatory Roles between m6A Modification and microRNAs.

N6-metyladenosine (m6A), one of the most common RNA methylation modifications in mammals, has attracted extensive attentions owing to its regulatory roles in a variety of physiological and pathological processes. As a reversible epigenetic modification on RNAs, m6A is dynamically mediated by the functional interplay among the regulatory proteins of methyltransferases, demethylases and methyl-binding proteins. In recent years, it has become increasingly clear that m6A modification is associated with the production and function of microRNAs (miRNAs). In this review, we summarize the specific kinds of m6A modification methyltransferases, demethylases and methyl-binding proteins. In particular, we focus on describing the roles of m6A modification and its regulatory proteins in the production and function of miRNAs in a variety of pathological and physiological processes. More importantly, we further discuss the mediating mechanisms of miRNAs in m6A modification and its regulatory proteins during the occurrence and development of various diseases.