DICP OpenIR
TRIP12 as a mediator of human papillomavirus/p16-related radiation enhancement effects
Wang, L.1; Zhang, P.1; Molkentine, D. P.1; Chen, C.1; Molkentine, J. M.1; Piao, H.1,2; Raju, U.1; Zhang, J.1; Valdecanas, D. R.1; Tailor, R. C.3; Thames, H. D.1; Buchholz, T. A.4; Chen, J.1; Ma, L.1; Mason, K. A.1; Ang, K-K1,4; Meyn, R. E.1; Skinner, H. D.4
Source PublicationONCOGENE
2017-02-09
ISSN0950-9232
DOI10.1038/onc.2016.250
Volume36Issue:6Pages:820-828
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectBiochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS Research AreaBiochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS KeywordSQUAMOUS-CELL CARCINOMA ; DOUBLE-STRAND BREAKS ; DNA-DAMAGE-RESPONSE ; P16 GENE ; CANCER GENOMICS ; POSITIVE HEAD ; NUCLEAR FOCI ; 53BP1 ; EXPRESSION ; REPAIR
AbstractPatients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) have better responses to radiotherapy and higher overall survival rates than do patients with HPV-negative HNSCC, but the mechanisms underlying this phenomenon are unknown. p16 is used as a surrogate marker for HPV infection. Our goal was to examine the role of p16 in HPV-related favorable treatment outcomes and to investigate the mechanisms by which p16 may regulate radiosensitivity. HNSCC cells and xenografts (HPV/p16-positive and -negative) were used. p16-overexpressing and small hairpin RNA-knockdown cells were generated, and the effect of p16 on radiosensitivity was determined by clonogenic cell survival and tumor growth delay assays. DNA double-strand breaks (DSBs) were assessed by immunofluorescence analysis of 53BP1 foci; DSB levels were determined by neutral comet assay; western blotting was used to evaluate protein changes; changes in protein half-life were tested with a cycloheximide assay; gene expression was examined by real-time polymerase chain reaction; and data from The Cancer Genome Atlas HNSCC project were analyzed. p16 overexpression led to downregulation of TRIP12, which in turn led to increased RNF168 levels, repressed DNA damage repair (DDR), increased 53BP1 foci and enhanced radioresponsiveness. Inhibition of TRIP12 expression further led to radiosensitization, and overexpression of TRIP12 was associated with poor survival in patients with HPV-positive HNSCC. These findings reveal that p16 participates in radiosensitization through influencing DDR and support the rationale of blocking TRIP12 to improve radiotherapy outcomes.
Language英语
WOS IDWOS:000394168200009
PublisherNATURE PUBLISHING GROUP
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/169523
Collection中国科学院大连化学物理研究所
Corresponding AuthorWang, L.
Affiliation1.Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Z7-3014,1515 Holcombe Blvd,Unit 1052, Houston, TX 77030 USA
2.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian, Peoples R China
3.Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA
4.Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA
Recommended Citation
GB/T 7714
Wang, L.,Zhang, P.,Molkentine, D. P.,et al. TRIP12 as a mediator of human papillomavirus/p16-related radiation enhancement effects[J]. ONCOGENE,2017,36(6):820-828.
APA Wang, L..,Zhang, P..,Molkentine, D. P..,Chen, C..,Molkentine, J. M..,...&Skinner, H. D..(2017).TRIP12 as a mediator of human papillomavirus/p16-related radiation enhancement effects.ONCOGENE,36(6),820-828.
MLA Wang, L.,et al."TRIP12 as a mediator of human papillomavirus/p16-related radiation enhancement effects".ONCOGENE 36.6(2017):820-828.
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