CENPM upregulation by E5 oncoprotein of human papillomavirus promotes radiosensitivity in head and neck squamous cell carcinoma

Liu, Tianyang1,2; Ma, Lin3; Song, Lianhao1; Yan, Bingqing5; Zhang, Siwei1; Wang, Bozhi1; Zuo, Nan1,2; Sun, Xinlei1; Deng, Yongqiang3; Ren, Qiushi2; Li, Yujun2; Zhou, Jingsong2; Liu, Qi2,8; Wei, Lanlan1,4,6,7,8

2022-06-01

10.1016/j.oraloncology.2022.105858

ORAL ONCOLOGY   影响因子和分区

1368-8375

1879-0593

Objectives: This study aims to investigate how human papillomavirus (HPV) affects the key gene in the biological behaviors of head and neck squamous cell carcinoma (HNSCC) that leads to better response to radiotherapy. Materials and Methods: The expression of key gene CENPM was analyzed using The Cancer Genome Atlas (TCGA) HNSCC data and HPV positive and HPV negative HNSCC tumors and cells. Assays with siRNAs, CRISPR/Cas9-based models, Western blot, qRT-PCR, ChIP, etc., were used to explore how HPV affects CENPM and response to radiotherapy for HNSCC. Results: CENPM occupies the hub in the HPV-related gene network. HPV-positive HNSCC showed higher level of CENPM expression comparing with HPV-negative HNSCC. HPV E5 has the most pronounced impact on CENPM (R = 0.44, p = 0.00081). This might result from the binding of transcription factor E2F1 to CENPM. We further found that inhibition of CENPM expression in HPV-positive HNSCC cell line SCC47 increased resistance to X-ray radiation by approximately 59% under 2 Gy irradiation, which may be resulted from a reduced proportion of mitotic cells. Conclusion: HPV E5 enhances CENPM expression by transcription factor E2F1 in HNSCC, which results in a radiosensitive profile in cell cycle redistribution of HNSCC. Thus, HPV infection in HNSCC provides profound evidence that underscores the magnitude of E2F1 control of CENPM expression illustrating the potential clinical benefit of CENPM examination for difficult-to-treat HPV-negative cancers.

HPV E5 CENPM Radiosensitivity Cell Cycle Head and neck cancer

SCI

英语

通讯

National Natural Science Foundation of China[82102822,82073007] ; Shenzhen Science and Technology RD Fund[JCYJ20210324131607019] ; Shenzhen Long-gang Fund for Science and Technology Project[LGKCYLWS2020101]

Oncology ; Dentistry, Oral Surgery & Medicine

Oncology ; Dentistry, Oral Surgery & Medicine

WOS:000804455300006

ELSEVIER

CLINICAL MEDICINE

Web of Science

1.Harbin Med Univ, Microbiol Dept, Harbin 150086, Heilongjiang, Peoples R China
2.Shenzhen Bay Lab, Shenzhen 518132, Guangdong, Peoples R China
3.Shenzhen Univ Gen Hosp, Dept Stomatol, Shenzhen 518055, Guangdong, Peoples R China
4.Shenzhen Southern Univ Sci & Technol, Natl Clin Res Ctr Infect Dis, Shenzhen 518000, Guangdong, Peoples R China
5.Nantong Ctr Dis Control & Prevent, Nantong 226007, Jiangsu, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Inst Hepatol, Shenzhen 518112, Guangdong, Peoples R China
7.Southern Univ Sci & Technol, Hosp Affiliated 2, Shenzhen 518000, Guangdong, Peoples R China
8.Shenzhen Third Peoples Hosp, Inst Hepatol, Natl Clin Res Ctr Infect Dis, Shenzhen 518112, Guangdong, Peoples R China

Liu, Tianyang,Ma, Lin,Song, Lianhao,et al. CENPM upregulation by E5 oncoprotein of human papillomavirus promotes radiosensitivity in head and neck squamous cell carcinoma[J]. ORAL ONCOLOGY,2022,129.

Liu, Tianyang.,Ma, Lin.,Song, Lianhao.,Yan, Bingqing.,Zhang, Siwei.,...&Wei, Lanlan.(2022).CENPM upregulation by E5 oncoprotein of human papillomavirus promotes radiosensitivity in head and neck squamous cell carcinoma.ORAL ONCOLOGY,129.

Liu, Tianyang,et al."CENPM upregulation by E5 oncoprotein of human papillomavirus promotes radiosensitivity in head and neck squamous cell carcinoma".ORAL ONCOLOGY 129(2022).