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bioRxiv · 10.1101/2022.05.31.494114

A novel 4 miRNA signature from salivary exosomes regulates multiple signalling pathways and predicts tumour progression in oral squamous cell carcinoma.

Patel, S.·Patel, A.·Mandlik, D.·Patel, K.·Swamy, K. B.·Tanavde, V.
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Abstract

Oral squamous cell carcinoma (OSCC) is often diagnosed late, leading to poor patient outcomes. This study aims to identify potential miRNA-based biomarkers for predicting disease progression using salivary exosomes derived from OSCC patients. Further, we identify crucial miRNA-mRNA networks involved in tumorigenesis and uncover the underlying mechanism responsible for OSCC progression. Small RNA (n=23) sequencing analysis along with data available from The Cancer Genome Atlas (TCGA) (n=114) identified 12 differentially expressed miRNAs in OSCC patients as compared to controls. Validating these findings, miR-140-5p, miR-143-5p, and miR-145-5p were significantly downregulated in a larger cohort of OSCC patients (n=70). This 3-miRNA signature demonstrated higher efficacy of salivary exosomes (p<0.0001) in early detection and clinically correlated with disease progression and overall survival of OSCC patients (p<0.05). Further, analysis of the transcriptome, TCGA datasets and miRNA-mRNA networks, identified top hub genes (HIF1a, CDH1, CD44, EGFR, and CCND1) which were regulated by a 3-miRNA signature. Based on pathway analysis, these miRNA-mRNA interactions were found to be involved in regulating epithelial-mesenchymal transition (EMT). Further, transfection-mediated upregulation of the 3-miRNA signature significantly decreased cell proliferation, induced apoptosis, resulted in G2/M phase cell cycle arrest and reduced the invasive and migratory potential by reversing the EMT process in OECM-1 cell line. Thus, this study identifies a 3-miRNA signature that can be utilized as a potential biomarker for early detection of OSCC and uncovers the underlying mechanisms responsible for converting a normal epithelial cell into a malignant phenotype.

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Patel, S., Patel, A., Mandlik, D., Patel, K., Swamy, K. B., Tanavde, V.. 2022-06-01. A novel 4 miRNA signature from salivary exosomes regulates multiple signalling pathways and predicts tumour progression in oral squamous cell carcinoma.. https://doi.org/10.1101/2022.05.31.494114

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