A novel 3-miRNA network regulates tumour progression in oral squamous cell carcinoma

Biomarker Research

Research

Aditi Patel¹  Krishna B.S Swamy¹  Shanaya Patel¹  Parina Patel¹  Vivek Tanavde²  Pooja Malaviya³  Kaustubh Patel⁴  Dushyant Mandlik⁴  Kaid Johar⁵ 

[1] Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, 380009, Ahmedabad, Gujarat, India;Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, 380009, Ahmedabad, Gujarat, India;Bioinformatics Institute, Agency for Science Technology and Research (A*STAR), Singapore, Singapore;Department of Cell and Molecular Biology, Iladevi Cataract and IOL Research Centre, Ahmedabad, Gujarat, India;Department of Head and Neck Oncology, HCG Cancer Centre, Ahmedabad, Gujarat, India;Department of Zoology, BMTC and Human Genetics, School of Sciences, Gujarat University, Ahmedabad, India;

关键词: Oral squamous cell carcinoma;    Salivary exosomes;    Exosomal miRNAs;    Biomarkers;    Disease progression;    Epithelial-mesenchymal transition;   

DOI  :  10.1186/s40364-023-00505-5

 received in 2023-02-06, accepted in 2023-05-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundLate diagnosis is one of the major confounders in oral squamous cell carcinoma (OSCC). Despite recent advances in molecular diagnostics, no disease-specific biomarkers are clinically available for early risk prediction of OSCC. Therefore, it is important to identify robust biomarkers that are detectable using non-invasive liquid biopsy techniques to facilitate the early diagnosis of oral cancer. This study identified potential salivary exosome-derived miRNA biomarkers and crucial miRNA-mRNA networks/underlying mechanisms responsible for OSCC progression.MethodsSmall RNASeq (n = 23) was performed in order to identify potential miRNA biomarkers in both tissue and salivary exosomes derived from OSCC patients. Further, integrated analysis of The Cancer Genome Atlas (TCGA) datasets (n = 114), qPCR validation on larger patient cohorts (n = 70) and statistical analysis with various clinicopathological parameters was conducted to assess the effectiveness of the identified miRNA signature. miRNA-mRNA networks and pathway analysis was conducted by integrating the transcriptome sequencing and TCGA data. The OECM-1 cell line was transfected with the identified miRNA signature in order to observe its effect on various functional mechanisms such as cell proliferation, cell cycle, apoptosis, invasive as well as migratory potential and the downstream signaling pathways regulated by these miRNA-mRNA networks.ResultsSmall RNASeq and TCGA data identified 12 differentially expressed miRNAs in OSCC patients compared to controls. On validating these findings in a larger cohort of patients, miR-140-5p, miR-143-5p, and miR-145-5p were found to be significantly downregulated. This 3-miRNA signature demonstrated higher efficacy in predicting disease progression and clinically correlated with poor prognosis (p < 0.05). Transcriptome, TCGA, and miRNA-mRNA network analysis identified HIF1a, CDH1, CD44, EGFR, and CCND1 as hub genes regulated by the miRNA signature. 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 the OECM-1 cell line.ConclusionsThus, this study identifies a 3-miRNA signature that can be utilized as a potential biomarker for predicting disease progression of OSCC and uncovers the underlying mechanisms responsible for converting a normal epithelial cell into a malignant phenotype.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2023_37_Article_IEq238.gif

41116_2023_37_Article_IEq227.gif

41116_2023_37_Article_IEq213.gif

Fig. 3

Fig. 1

41116_2023_37_Article_IEq109.gif