Tanavde, V. | bioRxiv Science

bioRxiv2022

Salivary exosomal miR-1307-5p predicts disease aggressiveness and poor prognosis in oral squamous cell carcinoma patients

BackgroundSalivary exosomal miRNAs as biomarkers facilitate repeated sampling, real-time disease monitoring and assessment of therapeutic response. This study identifies a single salivary exosomal miRNA prognosticator that will aid in improved patient outcome using a liquid biopsy approach. MethodSmall RNA and transcriptome sequencing profiles of tumour tissues and salivary exosomes from oral cancer patients were compared to their non-cancerous counterparts. We validated these results using the Cancer Genome Atlas database and performing Real-time PCR on a larger patient cohort. Potential target genes, miRNA-mRNA networks and enriched biological pathways regulated by this microRNA were identified using computational tools. ResultsSalivary exosomes (size: 30-50nm) demonstrated a strong expression of CD47 and detectable expression of tetraspanins CD63, CD81 and CD9 by flow cytometry. miR-1307-5p was exclusively overexpressed in tissues and salivary exosomes of oral cancer patients compared to their non-cancerous counterparts. Enhanced expression of miR-1307-5p clinically correlated with poor patient survival, disease progression, aggressiveness and chemo-resistance in these patients. Transcriptome analysis suggested that miRNA-1307-5p could promote oral cancer progression by suppressing THOP1, EHF, RNF4, GET4, and RNF114. ConclusionSalivary exosomal miRNA-1307-5p is a potential prognosticator for predicting poor survival and poor patient outcome in oral cancers.

cancer biology↗

bioRxiv2022

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

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.

cancer biology↗