School of Pharmacy, Binzhou Medical University, Yantai, China.
School of Biomedical Engineering, Dalian University of Technology, Dalian, China.
Front Cell Infect Microbiol. 2022 Jun 27;12:929666. doi: 10.3389/fcimb.2022.929666. eCollection 2022.
High-risk human papillomavirus infection may develop into a persistent infection that is highly related to the progression of various cancers, including cervical cancer and head and neck squamous cell carcinomas. The most common high-risk subtypes are HPV16 and HPV18. The oncogenic viral proteins expressed by high-risk HPVs E6/E7 are tightly involved in cell proliferation, differentiation, and cancerous transformation since E6/E7 mRNAs are derived from the same pre-mRNA. Hence, the alternative splicing in the E6/E7-coding region affects the balance of the E6/E7 expression level. Interrupting the balance of E6 and E7 levels results in cell apoptosis. Therefore, it is crucial to understand the regulation of E6/E7 splice site selection and the interaction of splicing enhancers and silencers with cellular splicing factors. In this review, we concluded the relationship of different E6/E7 transcripts with cancer progression, the known splicing sites, and the identified cis-regulatory elements within high-risk HPV E6/E7-coding region. Finally, we also reviewed the role of various splicing factors in the regulation of high-risk HPV oncogenic E6/E7 mRNA splicing.
高危型人乳头瘤病毒（HPV）感染可能发展为持续性感染，与多种癌症的进展高度相关，包括宫颈癌和头颈部鳞状细胞癌。最常见的高危亚型是 HPV16 和 HPV18。高危型 HPV 中表达的致癌病毒蛋白 E6/E7 紧密参与细胞增殖、分化和癌变，因为 E6/E7mRNA 来源于同一前体 mRNA。因此，E6/E7 编码区的选择性剪接影响 E6/E7 表达水平的平衡。打破 E6 和 E7 水平的平衡会导致细胞凋亡。因此，了解 E6/E7 剪接位点选择的调节以及剪接增强子和沉默子与细胞剪接因子的相互作用至关重要。在这篇综述中，我们总结了不同的 E6/E7 转录本与癌症进展、已知剪接位点以及高危型 HPV E6/E7 编码区中鉴定的顺式调节元件之间的关系。最后，我们还回顾了各种剪接因子在调节高危型 HPV 致癌 E6/E7mRNA 剪接中的作用。
