Pulliero Alessandra, Cassatella Giulia, Astuni Pietro, Khalid Zumama, Fiordoro Stefano, Izzotti Alberto
Department of Health Sciences, University of Genoa, 16132 Genoa, Italy.
Department of Internal Medicine and Medical Specialties, University of Genoa, 16132 Genoa, Italy.
Int J Mol Sci. 2024 Nov 26;25(23):12714. doi: 10.3390/ijms252312714.
Human papillomavirus (HPV) infection is a major etiologic factor in cervical cancer, a major cause of cancer-related morbidity and mortality among women worldwide. The role of microRNA (miRNA) dysregulation in cervical carcinogenesis is still largely unknown, but epigenetic changes, including DNA methylation and miRNA regulation, are crucial factors. The integration of HPV DNA into the host genome can lead to alterations in DNA methylation patterns and miRNA expression, contributing to the progression from normal epithelium to cervical intraepithelial neoplasia and, ultimately, to cervical cancer. This review aimed to examine the relationship between epigenetic changes in the development and progression of HPV associated with cervical cancer. A systematic literature search was conducted in major databases using predefined inclusion and exclusion criteria. Studies that investigated the expression, function, and clinical significance of miRNAs, DNA methylation, and the expression of oncoproteins in HPV-related cervical cancer were included. Data extraction, quality assessment, and synthesis were performed to provide a comprehensive overview of the current state of knowledge. We provide an overview of the studies investigating miRNA expression in relation to cervical cancer progression, highlighting their common outcomes and their weaknesses/strengths. To achieve this, we systematically searched the Pubmed database for all articles published between January 2018 and December 2023. Our systematic review revealed a substantial body of evidence supporting the pivotal role of miRNA dysregulation in the pathogenesis of HPV-related cervical cancer and related oncoproteins. From the 28 studies retrieved, miR-124, FAM194/miR-124-2, and DNA methylation are the most frequently down- or up-regulated in CC progression. Notably, FAM194/miR-124-2 and DNA methylation emerged as a promising molecular marker for distinguishing between cases requiring immediate surgical intervention and those amenable to a more conservative wait-and-see approach. This systematic review underscores the critical involvement of microRNA in the context of HPV-related cervical cancer and sheds light on the potential clinical utility of FAM194/miR-124-2 and DNA methylation as a discriminatory tool for guiding treatment decisions. The identification of patients who may benefit from early surgical intervention versus those suitable for observation has important implications for personalized and targeted management strategies in the era of precision medicine.
人乳头瘤病毒（HPV）感染是宫颈癌的主要病因，宫颈癌是全球女性癌症相关发病和死亡的主要原因。微小RNA（miRNA）失调在宫颈癌发生中的作用仍 largely unknown，但表观遗传变化，包括DNA甲基化和miRNA调控，是关键因素。HPV DNA整合到宿主基因组可导致DNA甲基化模式和miRNA表达改变，促使从正常上皮发展为宫颈上皮内瘤变，并最终发展为宫颈癌。本综述旨在研究与宫颈癌相关的HPV发展和进展过程中表观遗传变化之间的关系。使用预定义的纳入和排除标准在主要数据库中进行了系统的文献检索。纳入了研究miRNA、DNA甲基化的表达、功能及临床意义以及HPV相关宫颈癌中癌蛋白表达的研究。进行了数据提取、质量评估和综合分析，以全面概述当前的知识状况。我们概述了研究miRNA表达与宫颈癌进展关系的研究，突出了它们的共同结果以及优缺点。为实现这一目标，我们系统地在Pubmed数据库中搜索了2018年1月至2023年12月发表的所有文章。我们的系统综述揭示了大量证据支持miRNA失调在HPV相关宫颈癌发病机制及相关癌蛋白中的关键作用。从检索到的28项研究中，miR-124、FAM194/miR-124-2和DNA甲基化在宫颈癌进展中最常出现下调或上调。值得注意的是，FAM194/miR-124-2和DNA甲基化成为区分需要立即手术干预的病例和适合更保守观察等待方法的病例的有前景的分子标志物。本系统综述强调了微小RNA在HPV相关宫颈癌中的关键作用，并阐明了FAM194/miR-124-2和DNA甲基化作为指导治疗决策的鉴别工具的潜在临床应用。识别可能从早期手术干预中受益的患者与适合观察的患者，对精准医学时代的个性化和靶向管理策略具有重要意义。
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