MicroRNA sequencing reveals modulation of neurodegenerative miRNAs by <i>Withania somnifera</i> in human neuroblastoma SK-N-SH cells

OBJECTIVES: (WS) is known for its adaptogenic benefits; however, its beneficial effects in neurodegenerative diseases have not been fully explored. MicroRNAs (miRNAs) are small noncoding RNAs whose role(s) in modulating the effects of WS in neurodegeneration are yet unknown. This study aimed to investigate the impact of WS on miRNA expression in the SK-N-SH human neuroblastoma cell line. METHODS: We employed high-throughput sequencing to identify miRNAs with altered expression following dose-dependent and temporal treatment with WS. RESULTS: Our findings revealed that miRNA expression profiles were significantly altered in WS-treated cells. In the dose comparison (100 μg/mL vs. 50 μg/mL), 21 miRNAs were modulated at 3 h (18 upregulated and 3 downregulated), whereas 7 miRNAs were modulated at 9 h (3 upregulated and 4 downregulated). In the temporal comparison (9 h vs. 3 h), 9 miRNAs were modulated at 50 μg/mL (6 upregulated and 3 downregulated), whereas 30 miRNAs were modulated at 100 μg/mL (4 upregulated and 26 downregulated). Bioinformatics analyses, including target prediction and functional enrichment, revealed that these WS-modulated differentially expressed miRNAs were significantly enriched in neurodegenerative, apoptotic, and inflammatory pathways. Finally, 51 novel miRNAs were identified post-WS treatment. CONCLUSIONS: Taken together, our results indicate that WS may be beneficial in neurodegenerative disease and healthy aging by modulating noncoding miRNAs.