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Volume 11
Issue 3
10.3390/ncrna11030043
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Article

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

by
Daniel J. García
1,†,
Marco A. Pulpillo-Berrocal
1,†,
José L. Ruiz
1,2,
Eduardo Andrés-León
1,* and
Laura C. Terrón-Camero
1,*
1
Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN), Spanish National Research Council (CSIC), 18016 Granada, Spain
2
Functional Genomics Center Zurich, ETH Zurich, University of Zurich, 8057 Zurich, Switzerland
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Non-Coding RNA 2025, 11(3), 43; https://doi.org/10.3390/ncrna11030043
Submission received: 11 March 2025 / Revised: 22 May 2025 / Accepted: 4 June 2025 / Published: 9 June 2025
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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.
Keywords: de novo miRNAs; viral miRNAs; anal squamous cell carcinoma; squamous intraepithelial lesion; human papillomavirus; transcriptomics; target prediction; oncomiR de novo miRNAs; viral miRNAs; anal squamous cell carcinoma; squamous intraepithelial lesion; human papillomavirus; transcriptomics; target prediction; oncomiR

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MDPI and ACS Style

García, D.J.; Pulpillo-Berrocal, M.A.; Ruiz, J.L.; Andrés-León, E.; Terrón-Camero, L.C. Human Papillomavirus-Encoded microRNAs as Regulators of Human Gene Expression in Anal Squamous Cell Carcinoma: A Meta-Transcriptomics Study. Non-Coding RNA 2025, 11, 43. https://doi.org/10.3390/ncrna11030043

AMA Style

García DJ, Pulpillo-Berrocal MA, Ruiz JL, Andrés-León E, Terrón-Camero LC. Human Papillomavirus-Encoded microRNAs as Regulators of Human Gene Expression in Anal Squamous Cell Carcinoma: A Meta-Transcriptomics Study. Non-Coding RNA. 2025; 11(3):43. https://doi.org/10.3390/ncrna11030043

Chicago/Turabian Style

García, Daniel J., Marco A. Pulpillo-Berrocal, José L. Ruiz, Eduardo Andrés-León, and Laura C. Terrón-Camero. 2025. "Human Papillomavirus-Encoded microRNAs as Regulators of Human Gene Expression in Anal Squamous Cell Carcinoma: A Meta-Transcriptomics Study" Non-Coding RNA 11, no. 3: 43. https://doi.org/10.3390/ncrna11030043

APA Style

García, D. J., Pulpillo-Berrocal, M. A., Ruiz, J. L., Andrés-León, E., & Terrón-Camero, L. C. (2025). Human Papillomavirus-Encoded microRNAs as Regulators of Human Gene Expression in Anal Squamous Cell Carcinoma: A Meta-Transcriptomics Study. Non-Coding RNA, 11(3), 43. https://doi.org/10.3390/ncrna11030043

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