Roles of N6-methyladenosine in LncRNA changes and oxidative damage in cadmium-induced pancreatic β-cells

N6-methyladenosine (m6A) modification and LncRNAs play crucial regulatory roles in various pathophysiological processes, yet roles of m6A modification and the relationship between m6A modification and LncRNAs in cadmium-induced oxidative damage of pancreatic β-cells have not been fully elucidated. In this study, m6A agonist entacapone and inhibitor 3-deazadenosine were used to identify the effects of m6A on cadmium-induced oxidative damage as well as LncRNA changes. Our results indicate that elevated levels of m6A modification by entacapone can rescue the cell viability and attenuate the cell apoptosis, while the inhibition levels of m6A modification can exacerbate the cell death. Furthermore, the elevation of m6A modification can recover cadmium-induced oxidative damage to pancreatic β-cells, which characterized as inhibition the ROS accumulation, MDA contents, protein expressions of Nrf2 and Ho-1, while elevation the expressions of Sod1 and Gclc. On the contrary, the reduction levels of m6A modification can exacerbate the cadmium-induced oxidative damage. More importantly, six significantly differentially expressed LncRNAs were selected according to our preliminary sequencing data (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253072) and there is a clear correlation between the levels of these LncRNAs and m6A modification after cadmium treatment. Interestingly, the intervention of m6A modification levels can significantly affect the levels of these LncRNAs. In detail, the stimulation of m6A modification reversed the changes of cadmium-induced LncRNAs, while the m6A modification inhibition can significantly exacerbate the changes of cadmium-induced LncRNAs. In conclusion, our data revealed critical roles of m6A modification in cadmium-induced LncRNAs and oxidative damage. Our findings point to a new direction for future studies on the molecular mechanisms of pancreatic β-cell damage induced by cadmium.