Department of Dermatology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
PeerJ. 2024 May 20;12:e17376. doi: 10.7717/peerj.17376. eCollection 2024.
Condyloma acuminatum (CA) is caused by low-risk human papillomavirus, and is characterized by high recurrence after treatment. The RNA modification N6-methyladenosine (m6A) plays an important role during diverse viral infections, including high-risk HPV infection in cervical cancer. However, it is unclear whether low-risk HPV infection changes the RNA m6A methylation in CA.
High-throughputm6A-sequencing was performed to profile the transcriptome-wide mRNA modifications of CA tissues infected by LR-HPVs and the paired normal tissues from CA patients. We further investigated the regulation of alternative splicing by RNA binding proteins (RBPs) with altered m6A modification and constructed a regulatory network among these RBPs, regulated alternative splicing events (RASEs) and regulated alternative splicing genes (RASGs) in CA.
The results show that the m6A level in CA tissues differed from that in the paired controls. Furthermore, cell cycle- and cell adhesion- associated genes with m6A modification were differentially expressed in CA tissues compared to the paired controls. In particular, seven RNA binding protein genes with specific m6A methylated sites, showed a higher or lower expression at the mRNA level in CA tissues than in the paired normal tissues. In addition, these differentially expressed RNA binding protein genes would regulate the alternative splicing pattern of apoptotic process genes in CA tissue.
Our study reveals a sophisticated m6A modification profile in CA tissue that affects the response of host cells to HPV infection, and provides cues for the further exploration of the roles of m6A and the development of a novel treatment strategy for CA.
尖锐湿疣（CA）由低危型人乳头瘤病毒（HPV）引起，其特点是治疗后复发率高。RNA 修饰 N6-甲基腺苷（m6A）在多种病毒感染中发挥重要作用，包括宫颈癌中的高危 HPV 感染。然而，低危型 HPV 感染是否会改变 CA 中的 RNA m6A 甲基化尚不清楚。
通过高通量 m6A 测序，对受 LR-HPV 感染的 CA 组织和 CA 患者配对的正常组织进行全转录组 mRNA 修饰谱分析。我们进一步研究了 RNA 结合蛋白（RBPs）中改变的 m6A 修饰对可变剪接的调节作用，并构建了这些 RBPs、调节可变剪接事件（RASEs）和 CA 中调节可变剪接基因（RASGs）之间的调控网络。
结果表明，CA 组织中的 m6A 水平与配对对照组不同。此外，与配对对照组相比，CA 组织中与细胞周期和细胞黏附相关的基因的 m6A 修饰存在差异表达。特别是，在 CA 组织中，有七个具有特定 m6A 甲基化位点的 RNA 结合蛋白基因的 mRNA 水平表达高于或低于配对正常组织。此外，这些差异表达的 RNA 结合蛋白基因会调节 CA 组织中凋亡过程基因的可变剪接模式。
本研究揭示了 CA 组织中复杂的 m6A 修饰谱，影响宿主细胞对 HPV 感染的反应，为进一步探索 m6A 的作用和开发 CA 的新治疗策略提供了线索。
