Biology subjects

Tanavde, V.

Publications and source records attributed to Tanavde, V..

3 recordsLinked to original sources

bioRxiv2026

Inhibition of miR-1307 Reverses Resistance to Cisplatin in Drug-Resistant Oral Squamous Cell Carcinoma

BackgroundChemo-resistance remains a major clinical challenge in Oral Squamous Cell Carcinoma (OSCC), attributed to the intrinsically resistant cells. Although tumour-derived extracellular vesicles (EVs) have been implicated in cell-cell communication, their role in propagating chemo-resistance remains poorly defined. This study aims to identify salivary EV-associated miRNAs capable of predicting chemoresistance and to delineate the role of miR-1307-5p in modulating CSC-driven therapeutic refractoriness. MethodsSalivary EV-derived expression profile of miR-1307-5p was assessed by qPCR in chemo resistant OSCC patients and further validated in TCGA small RNA sequencing datasets. Expression was validated by qPCR and correlated with clinicopathological outcomes. Functional assays including cell-cycle analysis, apoptosis, migration/invasion, 3D spheroids, angiogenesis, and CAM assays were performed in miR-1307-5p inhibited CD44 CSC subpopulation compared to its vehicular control. Transcriptomic profiling cross-referencing with TCGA was conducted to identify potential novel targets of miR-1307-5p. Chemo-sensitisation was assessed by treating the knockdown chemo resistant cells with low dose cisplatin and validating it using in-vitro functional assays and orthotopic xenograft model. ResultsmiR-1307-5p was significantly elevated in salivary EVs of chemo resistant OSCC patients and correlated with poor overall survival (p = 0.03). The miRNA was markedly enriched in endogenously resistant CD44 CSCs. Silencing of miR-1307-5p induced G2/M arrest, triggered apoptosis, impaired invasion, and reduced angiogenesis both in-vitro and in ex-vivo assays. Transcriptomic profiling, TCGA validation, and integrative pathway analysis identified key oncogenic hubs which converge on PI3K-AKT, MAPK/ERK, and YAP signalling pathways governing EMT. Inhibition of miR-1307-5p restored cisplatin sensitivity in resistant CSCs, with low-dose cisplatin producing substantial tumour suppression in-vitro and in-vivo. Reduced CD44 expression in xenograft models confirmed CSC reprogramming. EVs from anti-miR-treated cells confer chemo sensitisation upon uptake by resistant CSCs. Xenograft models substantiated that EVs can initiate tumour formation and that EV-mediated delivery of anti-miR-1307-5p drives significant tumour regression. ConclusionThis study identifies salivary EV-derived miR-1307-5p as a clinically relevant biomarker of chemoresistance in OSCC and reveals its mechanistic role in sustaining CSC-driven therapeutic failure. Targeting miR-1307-5p offers a promising avenue for restoring cisplatin sensitivity and developing exosome-based therapeutic strategies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/709730v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@19f88e0org.highwire.dtl.DTLVardef@d36b95org.highwire.dtl.DTLVardef@3c2579org.highwire.dtl.DTLVardef@c04ef5_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

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↗