# cGAS-STING Pathway-Induced BST2 Enhances HPV-Infected Keratinocyte Proliferation in Condyloma Acuminata

## TL;DR

This study shows that BST2, a gene activated by the cGAS-STING pathway, promotes the growth of HPV-infected skin cells in genital warts, suggesting it could be a new treatment target.

## Contribution

The study reveals a novel role of BST2 in HPV-induced keratinocyte proliferation through the cGAS-STING and MEK/ERK/c-Myc pathways.

## Key findings

- BST2 is significantly upregulated in CA lesions and HPV-infected keratinocytes via the cGAS/STING pathway.
- BST2 promotes keratinocyte proliferation through the MEK/ERK/c-Myc pathway.
- BST2 knockdown significantly inhibits this proliferative effect.

## Abstract

Background: Condyloma acuminata (CA) is a common sexually transmitted disease caused by human papillomavirus (HPV). Abnormal keratinocyte proliferation is a hallmark of CA, but the underlying mechanisms remain unclear. BST2, an interferon-stimulated gene, is implicated in viral inhibition and tumor cell proliferation. This study aimed to investigate whether BST2 is involved in HPV-induced keratinocyte proliferation. Methods: We conducted bioinformatics analysis using publicly available datasets from the Gene Expression Omnibus (GEO) to assess BST2 expression in CA. HPV-6/11 live virus and HPV11-E7 lentiviruses were used to infect HaCaT cells to mimic early HPV infection and viral genome integration. We examined BST2 expression in both CA patient tissue samples and in vitro models using RT-qPCR, Western blot, and immunohistochemistry. To investigate the signaling mechanisms, we used siRNA to knock down key components of the cGAS/STING pathway and examined BST2 expression levels. Additionally, we assessed keratinocyte proliferation through CCK-8 assays and cell counting. Activation of downstream signaling pathways was evaluated using Western blot analysis for key molecules in the MEK/ERK/c-Myc pathway. Results: BST2 was significantly upregulated in CA lesions and HPV-infected keratinocytes through the cGAS/STING pathway. BST2 activation promoted keratinocyte proliferation via the MEK/ERK/c-Myc pathway, and this effect was significantly inhibited by BST2 knockdown. Conclusions: HPV could promote the proliferation of keratinocytes from condyloma acuminata lesions through inducing BST2, indicating that BST2 would be a potential therapeutic target for condyloma acuminata.