期刊
SEMINARS IN CANCER BIOLOGY
卷 86, 期 -, 页码 482-496出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2022.02.014
关键词
Papillomavirus; Splicing; Polyadenylation; hnRNP; SR protein; Akt; DDR
类别
资金
- Swedish Research Council -Medicine
- Swedish Cancer Society
- [VR2019-01210]
- [CAN2018/702]
This review highlights the importance of RNA-binding proteins in controlling HPV gene expression, particularly in regulating the oncogenic E6 and E7 genes and immunogenic L1 and L2 proteins, which play a role in immune evasion during carcinogenesis.
Human papillomaviruses (HPV) are epitheliotropic DNA tumor viruses that are prevalent in the human popu-lation. A subset of the HPVs termed high-risk HPVs (HR-HPVs) are causative agents of anogenital cancers and head-and-neck cancers. Cancer is the result of persistent high-risk HPV infections that have not been cleared by the immune system of the host. These infections are characterized by dysregulated HPV gene expression, in particular constitutive high expression of the HPV E6 and E7 oncogenes and absence of the highly immunogenic viral L1 and L2 capsid proteins. HPVs make extensive use of alternative mRNA splicing to express its genes and are therefore highly dependent on cellular RNA-binding proteins for proper gene expression. Levels of RNA -binding proteins are altered in HPV-containing premalignant cervical lesions and in cervical cancer. Here we review our current knowledge of RNA-binding proteins that control HPV gene expression. We focus on RNA -binding proteins that control expression of the E6 and E7 oncogenes since they initiate and drive develop-ment of cancer and on the immunogenic L1 and L2 proteins as there silencing may contribute to immune evasion during carcinogenesis. Furthermore, cellular RNA-binding proteins are essential for HPV gene expression and as such may be targets for therapy to HPV infections and HPV-driven cancers.
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