Agarwal Mohini, Kumar Manish, Dahiya Sarthak, Kumar Anoop, Tripathi Rupal, Bala Kumud
Therapeutics and Molecular Diagnostic Lab, J-3 Block, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India.
Amity Institute of Pharmacy, Amity University, Noida, India.
Sci Rep. 2025 Aug 22;15(1):30837. doi: 10.1038/s41598-025-05599-5.
Cervical cancer is a prevalent malignancy worldwide and represents a significant health burden for women. Toll-like receptors (TLRs) are crucial components of the innate immune system and play a vital role in recognizing pathogen-associated molecular patterns. Among the TLRs, TLR3 has been implicated in the defense against viral infections, including human papillomavirus (HPV), the primary etiological agent of cervical cancer. Missense single-nucleotide polymorphisms (SNPs) in the TLR3 gene can alter its protein structure and potentially influence its function, leading to variations in immune responses and disease susceptibility. This study aimed to investigate the impact of TLR3 missense SNPs on cervical cancer development through in silico methods. A comprehensive analysis was performed using various computational tools and databases to predict the functional consequences of identified TLR3 missense SNPs. The selection criteria for SNPs included their reported association with cervical cancer or their potential effects on TLR3 structure and function. Three extremely detrimental TLR-3 nsSNPs, namely N284I (rs5743316), C37R(rs752889035), and L360P(rs768091235), have been found among the 150 nsSNPs that have so far been reported in the dbSNP database. The in silico analysis suggests that these genetic variations may contribute to the development and progression of cervical cancer by modulating TLR3 function. Further experimental studies are warranted to validate these findings and elucidate the underlying mechanisms, which may aid in developing novel therapeutic strategies for cervical cancer prevention and treatment.
宫颈癌是全球范围内一种常见的恶性肿瘤，对女性健康构成重大负担。Toll样受体（TLRs）是先天免疫系统的关键组成部分，在识别病原体相关分子模式方面发挥着至关重要的作用。在TLRs中，TLR3参与了针对包括人乳头瘤病毒（HPV）在内的病毒感染的防御，HPV是宫颈癌的主要病原体。TLR3基因中的错义单核苷酸多态性（SNPs）可改变其蛋白质结构，并可能影响其功能，导致免疫反应和疾病易感性的差异。本研究旨在通过计算机模拟方法研究TLR3错义SNPs对宫颈癌发生发展的影响。使用各种计算工具和数据库进行了全面分析，以预测已鉴定的TLR3错义SNPs的功能后果。SNPs的选择标准包括其与宫颈癌的报道关联或其对TLR3结构和功能的潜在影响。在dbSNP数据库中迄今报道的150个非同义单核苷酸多态性（nsSNPs）中，发现了三个极其有害的TLR-3 nsSNPs，即N284I（rs5743316）、C37R（rs752889035）和L360P（rs768091235）。计算机模拟分析表明，这些基因变异可能通过调节TLR3功能促进宫颈癌的发生和发展。有必要进行进一步的实验研究来验证这些发现并阐明潜在机制，这可能有助于开发预防和治疗宫颈癌的新治疗策略。
