Human Papillomavirus-Encoded microRNAs as Regulators of Human Gene Expression in Anal Squamous Cell Carcinoma: A Meta-Transcriptomics Study.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-Coding RNA Pub Date : 2025-06-09 DOI:10.3390/ncrna11030043

Daniel J García, Marco A Pulpillo-Berrocal, José L Ruiz, Eduardo Andrés-León, Laura C Terrón-Camero

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引用次数: 0

Abstract

Introduction: Anal squamous cell carcinoma (ASCC) is a rare but increasingly common gastrointestinal malignancy, mainly associated with oncogenic human papillomaviruses (HPVs). The role of non-coding RNAs (ncRNAs) in tumorigenesis is recognized, but the impact of viral ncRNAs on host gene expression remains unclear. Methods: We re-analyzed total RNA-Seq data from 70 anal biopsies: 31 low-grade squamous intraepithelial lesions (LGSIL), 16 high-grade SIL (HGSIL), and 23 ASCC cases. Microbial composition was assessed taxonomically. Novel viral miRNAs were predicted using vsRNAfinder and linked to host targets using TargetScan and expression correlation analyses. Results: Microbial profiling revealed significant differences in abundance, with Alphapapillomaviruses types 9, 10, and 14 enriched across lesion grades. We identified 90 novel viral miRNAs and 177 significant anti-correlated miRNA-mRNA interactions. Target genes were enriched in pathways related to cell cycle, epithelial-mesenchymal transition, lipid metabolism, immune modulation, and viral replication. Discussion: Our findings suggest that HPV-derived miRNAs, including those from low-risk types, may contribute to neoplastic transformation by modulating host regulatory networks. Conclusion: This study highlights viral miRNAs as potential drivers of HPV-related anal cancer and supports their utility as early biomarkers and therapeutic targets in ASCC.

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人乳头瘤病毒编码的microrna作为肛门鳞状细胞癌中人类基因表达的调节因子：一项meta转录组学研究。

简介：肛门鳞状细胞癌（ASCC）是一种罕见但日益常见的胃肠道恶性肿瘤，主要与致瘤性人乳头瘤病毒（hpv）相关。非编码rna （ncRNAs）在肿瘤发生中的作用是公认的，但病毒ncRNAs对宿主基因表达的影响尚不清楚。方法：我们重新分析了70例肛门活检的总RNA-Seq数据：31例低级别鳞状上皮内病变（LGSIL）， 16例高级别鳞状上皮内病变（HGSIL）和23例ASCC。微生物组成进行了分类分析。使用vsRNAfinder预测新的病毒mirna，并使用TargetScan和表达相关性分析将其与宿主靶标连接。结果：微生物谱显示了显著的丰度差异，在不同的病变级别中，9型、10型和14型甲型乳头瘤病毒富集。我们鉴定了90个新的病毒mirna和177个显著的抗相关miRNA-mRNA相互作用。靶基因在细胞周期、上皮-间质转化、脂质代谢、免疫调节和病毒复制等相关通路中富集。讨论：我们的研究结果表明，hpv衍生的mirna，包括那些来自低风险类型的mirna，可能通过调节宿主调节网络来促进肿瘤转化。结论：本研究强调了病毒mirna作为hpv相关肛门癌的潜在驱动因素，并支持其作为ASCC早期生物标志物和治疗靶点的效用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.