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MiRNA genetic variations associated with the predisposition of oral squamous cell carcinoma in central Indian population.

ABSTRACT: The disease burden of Oral Squamous Cell Carcinoma (OSCC) is rising day-by-day and is expected to rise 62 % through 2035. The chewing of tobacco, areca nut, and betel leaf, poor oral hygiene, and chronic infection are common risk factors of OSCC, but genetic and epigenetic factors also contribute equally. MicroRNAs (miRNAs) are comprised of small, non-coding endogenous RNA that regulate a plethora of biological activities by targeting messenger RNA through degradation or inhibition. Single Nucleotide Polymorphisms (SNPs) in miRNA genes can regulate the development and progression of OSCC. The present study aimed to determine the association between SNPs in miRNA genes (miRSNPs) with the risk of OSCC. A case-control study involving 225 histo-pathologically confirmed OSCC cases and 225 healthy controls was conducted, where 25 miRSNPs were analyzed by iPLEX MassArray analysis. A SNP rs12220909 in MIR4293 showed a highly protective effect (CC vs GG, OR = 0.0431, 95%CI = 0.005-0.323, p = 3e-6). Whereas three SNPs, namely, rs4705342 in MIR143 (CC vs TT, OR = 2.25, 95%CI = 2.00-2.53, p = 0.0008), rs531564 in MIR124 (CC vs GG, OR = 24.18, 95%CI = 3.22-181.37, p = 3e-6), and rs3746444 in MIR499 (AA vs GG, OR = 2.01, 95%CI = 1.32-3.05, p = 0.001) were significantly associated with a higher risk of OSCC. Additionally, NanoString-based nCounter miRNA expression profiling revealed that miR-499a (Log2FC = -1.07), and miR-143 (Log2FC = -1.56) were aberrantly expressed in OSCC tissue. Taken together, the above miSNPs may contribute to the high incidence of OSCC in central India. However, further studies with large cohorts and ethnic stratification are required to validate our findings.

SUBMITTER: Tiwari S

PROVIDER: S-EPMC11315085 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature

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miRNA genetic variations associated with the predisposition of oral squamous cell carcinoma in central Indian population.

Tiwari Shikha S Pandey Ritu R Kumar Vinay V Das Saikat S Gupta Vikas V Nema Rajeev R Kumar Ashok A

Non-coding RNA research 20240714 4

The disease burden of Oral Squamous Cell Carcinoma (OSCC) is rising day-by-day and is expected to rise 62 % through 2035. The chewing of tobacco, areca nut, and betel leaf, poor oral hygiene, and chronic infection are common risk factors of OSCC, but genetic and epigenetic factors also contribute equally. MicroRNAs (miRNAs) are comprised of small, non-coding endogenous RNA that regulate a plethora of biological activities by targeting messenger RNA through degradation or inhibition. Single Nucle ...[more]

PMID: 39131689

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Project description: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.

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MiRNA genetic variations associated with the predisposition of oral squamous cell carcinoma in central Indian population.

Publications

miRNA genetic variations associated with the predisposition of oral squamous cell carcinoma in central Indian population.

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