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.