PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■尖锐湿疣（CA）是由低危型人乳头瘤病毒引起的，治疗后复发率高。RNA修饰N6-甲基腺苷（m6A）在多种病毒感染中起着重要作用，包括宫颈癌中的高危型HPV感染。然而,目前尚不清楚低危HPV感染是否会改变CA中RNAm6A甲基化.
■进行高通量m6A测序，以分析被LR-HPV感染的CA组织和CA患者配对的正常组织的转录组范围的mRNA修饰。我们进一步研究了具有改变的m6A修饰的RNA结合蛋白（RBPs）对可变剪接的调节，并在这些RBPs之间构建了一个调节网络。CA中的调控可变剪接事件(RASEs)和调控可变剪接基因(RASGs)。
■结果显示CA组织中的m6A水平与配对对照中的m6A水平不同。此外，与配对对照相比，具有m6A修饰的细胞周期和细胞粘附相关基因在CA组织中差异表达。特别是,七个具有特定m6A甲基化位点的RNA结合蛋白基因，CA组织中mRNA水平的表达高于或低于配对的正常组织。此外,这些差异表达的RNA结合蛋白基因将调节CA组织中凋亡过程基因的可变剪接模式。
■我们的研究揭示了CA组织中复杂的m6A修饰特征，影响宿主细胞对HPV感染的反应，并为进一步探索m6A的作用和开发新的CA治疗策略提供了线索。
■进行高通量m6A测序，以分析被LR-HPV感染的CA组织和CA患者配对的正常组织的转录组范围的mRNA修饰。我们进一步研究了具有改变的m6A修饰的RNA结合蛋白（RBPs）对可变剪接的调节，并在这些RBPs之间构建了一个调节网络。CA中的调控可变剪接事件(RASEs)和调控可变剪接基因(RASGs)。
■结果显示CA组织中的m6A水平与配对对照中的m6A水平不同。此外，与配对对照相比，具有m6A修饰的细胞周期和细胞粘附相关基因在CA组织中差异表达。特别是,七个具有特定m6A甲基化位点的RNA结合蛋白基因，CA组织中mRNA水平的表达高于或低于配对的正常组织。此外,这些差异表达的RNA结合蛋白基因将调节CA组织中凋亡过程基因的可变剪接模式。
■我们的研究揭示了CA组织中复杂的m6A修饰特征，影响宿主细胞对HPV感染的反应，并为进一步探索m6A的作用和开发新的CA治疗策略提供了线索。
