miRNA99a as a Potential target in P13K/Akt1/mTOR signaling pathway in progression of OSCC

Abstract

Background

Oral cancer presents a significant global health challenge, driving ongoing research to enhance diagnostics and treatments. MicroRNAs, particularly miRNA99a, have emerged as key players in oral cancer's initiation, progression, and advanced development. However, their precise molecular mechanisms remain unclear. We analyze miRNA99a in modulating the PI3K/Akt1/mTOR signaling pathway within oral squamous cell carcinoma through in silico data analysis. Additionally, we examined miRNA99a levels in both oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC).

Materials and methods

A comprehensive approach utilizing various insilico tools identified potential target genes regulated by miRNA99a and examined their interactions within the PI3K/Akt1/mTOR signaling pathway. The study involved meticulous screening, functional enrichment analyses, and network analyses to understand the regulatory networks influenced by miRNA99a. Additionally, RT-PCR was used to measure the CT levels of miR-99a in OSMF, OSCC and NM samples.

Results

The analysis revealed a cohort of putative target genes regulated by miRNA99a, demonstrating their involvement in crucial cellular processes linked to OSCC progression. Functional enrichment analyses highlighted the significant association of these target genes with the PI3K/Akt1/mTOR pathway, indicating their potential impact on pivotal oncogenic signaling pathways. Network analyses revealed complex regulatory networks orchestrated by miRNA99a, its action within the PI3K/Akt1/mTOR signalling pathway and influencing OSCC development. RT-PCR analysis revealed a significant downregulation of miR-99a in OSCC and OSMF samples compared to NM, with mean CT values of 39.0940 and 38.3986 respectively, versus 33.7540 in NM (p = 0.000).

Conclusion

miRNA99a′s potential as a crucial regulator of the PI3K/Akt1/mTOR pathway in OSCC. The identified target genes and their interactions offer a foundation for further experimental validations, presenting opportunities for discovering novel therapeutic avenues or prognostic markers in managing OSCC. Integrating multi-omics data reinforces the significance of miRNA99a-mediated regulatory mechanisms in the intricate landscape of oral cancer biology.