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

## TL;DR

This study explores how human papillomavirus microRNAs affect gene expression in anal cancer, suggesting they may play a role in cancer development.

## Contribution

Identifies novel viral miRNAs and their anti-correlated host targets in anal squamous cell carcinoma.

## Key findings

- Alphapapillomaviruses types 9, 10, and 14 are enriched in anal lesions across different grades.
- 90 novel viral miRNAs and 177 significant miRNA–mRNA interactions were identified.
- Target genes are involved in cell cycle, immune modulation, and viral replication pathways.

## 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.