Integrative assessment of RNA sequencing and in silico analysis to pinpoint mRNAs, lncRNAs, and circRNAs interactions with miRNAs underlying arsenic-induced neurotoxicity.

Background: The acquisition of neurodegeneration hallmarks necessitates molecular changes at multiple levels of functional genomics. Regulatory RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play crucial roles in modulating messenger RNAs (mRNAs) expression and are potential molecules that regulate multifactorial neurotoxicity mechanisms. Integrated studies of regulatory RNAs' functions are still lacking to portray the complete picture. In this study, we carried out a detailed analysis of mRNA, lncRNA, and circRNA profiles in differentiated SH-SY5Y cells exposed to arsenic, a well-known neurotoxicant, using the Illumina Novaseq6000 platform. Subsequently, employing a bioinformatics approach, we identified specific interactions between these RNA molecules and potential miRNAs, unraveling intricate regulatory networks.

Results: Among significantly deregulated transcripts, we identified 2487 mRNA transcripts, 1192 lncRNA transcripts, and 20 circRNA transcripts in arsenic-treated cells compared to control. Functional enrichment analysis indicated their involvement in numerous pathways underlying neurotoxicity. Further, these regulatory molecules displayed strong interactions with multiple miRNAs implicated in neuronal damage.

Conclusion: Our findings revealed intricate molecular alterations in response to arsenic exposure, emphasizing the crucial role of multi-omics technologies in understanding neurodegeneration. This approach has enabled the identification of potential targets for future exploration, emphasizing the precise modulation of regulatory RNA networks to mitigate the effects of arsenic.