cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro
Abstract Background High-risk human papillomaviruses are the causal agents of a subset of head and neck cancers. A previous transcriptomic analysis showed that cIAP2 protein, involved in cell survival and apoptosis, is upregulated in OKF6 oral cells that express HPV16 E6/E7. In addition, cIAP2 promo...
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BMC
2024-09-01
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| Series: | Infectious Agents and Cancer |
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| Online Access: | https://doi.org/10.1186/s13027-024-00609-z |
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| author | Carolina Oliva Diego Carrillo-Beltrán Julio C. Osorio Iván Gallegos Felipe Carvajal Claudio Mancilla-Miranda Paul Boettiger Enrique Boccardo Francisco Aguayo |
| author_facet | Carolina Oliva Diego Carrillo-Beltrán Julio C. Osorio Iván Gallegos Felipe Carvajal Claudio Mancilla-Miranda Paul Boettiger Enrique Boccardo Francisco Aguayo |
| author_sort | Carolina Oliva |
| collection | DOAJ |
| description | Abstract Background High-risk human papillomaviruses are the causal agents of a subset of head and neck cancers. A previous transcriptomic analysis showed that cIAP2 protein, involved in cell survival and apoptosis, is upregulated in OKF6 oral cells that express HPV16 E6/E7. In addition, cIAP2 promotes radioresistance, a very important concern in HNC treatment. However, cIAP2 increase has not yet been evaluated in oropharyngeal carcinomas (OPCs), nor has been the role of cIAP2 in HNC radioresistance. Methods We carried out a descriptive-analytical retrospective study in 49 OPCs from Chilean patients. We determined the expression of cIAP2 at transcript and proteins levels using reverse-transcriptase -polymerase chain reaction and immunohistochemistry, respectively. HPV and p16 expression were previously analyzed in these specimens. In addition, SCC-143 HNC cells ectopically expressing HPV16 E6/E7 were analyzed for cIAP2 expression and after transfection with a siRNA for HPV16 E6/E7 knocking down. Results We found a statistically significant association between HPV presence and cIAP2 expression (p = 0.0032 and p = 0.0061, respectively). An association between p16 and cIAP2 levels was also found (p = 0.038). When SCC-143 cells were transfected with a construct expressing HPV16 E6/E7, the levels of cIAP2 were significantly increased (p = 0.0383 and p = 0.0115, respectively). Conversely, HPV16 E6 and E7 knocking down resulted in a decrease of cIAP2 levels (p = 0.0161 and p = 0.006, respectively). Finally, cIAP2 knocking down in HPV16 E6/E7 cells resulted in increased apoptosis after exposure to radiation at 4 and 8 Gy (p = 0.0187 and p = 0.0061, respectively). Conclusion This study demonstrated for the first time a positive relationship between HPV presence and cIAP2 levels in OPCs. Additionally, cIAP2 knocking down sensitizes HNC cells to apoptosis promoted by radiation. Therefore, cIAP2 is a potential therapeutic target for radiation in HPV-driven HNC. |
| format | Article |
| id | doaj-art-7ea0dcc5de4d462cadf7280be93b89b5 |
| institution | OA Journals |
| issn | 1750-9378 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | BMC |
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| series | Infectious Agents and Cancer |
| spelling | doaj-art-7ea0dcc5de4d462cadf7280be93b89b52025-08-20T01:49:46ZengBMCInfectious Agents and Cancer1750-93782024-09-0119111210.1186/s13027-024-00609-zcIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitroCarolina Oliva0Diego Carrillo-Beltrán1Julio C. Osorio2Iván Gallegos3Felipe Carvajal4Claudio Mancilla-Miranda5Paul Boettiger6Enrique Boccardo7Francisco Aguayo8Laboratorio de Oncovirología, Programa de Virología, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de ChileInstituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de ChileLaboratorio de Oncovirología, Programa de Virología, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de ChileDepartamento Anatomía Patológica, Hospital Clínico Universidad de ChileDepartamento de Oncología Básico Clínica, Facultad de Medicina, Universidad de ChileServicio de Radioterapia, Instituto Nacional del CáncerDepartamento de Otorrinolaringología, Hospital Clínico Universidad de ChileLaboratory of Oncovirology, Department of Microbiology, Instituto de Ciências Biomédicas, Universidade de São PauloLaboratorio de Oncovirología, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad de TarapacáAbstract Background High-risk human papillomaviruses are the causal agents of a subset of head and neck cancers. A previous transcriptomic analysis showed that cIAP2 protein, involved in cell survival and apoptosis, is upregulated in OKF6 oral cells that express HPV16 E6/E7. In addition, cIAP2 promotes radioresistance, a very important concern in HNC treatment. However, cIAP2 increase has not yet been evaluated in oropharyngeal carcinomas (OPCs), nor has been the role of cIAP2 in HNC radioresistance. Methods We carried out a descriptive-analytical retrospective study in 49 OPCs from Chilean patients. We determined the expression of cIAP2 at transcript and proteins levels using reverse-transcriptase -polymerase chain reaction and immunohistochemistry, respectively. HPV and p16 expression were previously analyzed in these specimens. In addition, SCC-143 HNC cells ectopically expressing HPV16 E6/E7 were analyzed for cIAP2 expression and after transfection with a siRNA for HPV16 E6/E7 knocking down. Results We found a statistically significant association between HPV presence and cIAP2 expression (p = 0.0032 and p = 0.0061, respectively). An association between p16 and cIAP2 levels was also found (p = 0.038). When SCC-143 cells were transfected with a construct expressing HPV16 E6/E7, the levels of cIAP2 were significantly increased (p = 0.0383 and p = 0.0115, respectively). Conversely, HPV16 E6 and E7 knocking down resulted in a decrease of cIAP2 levels (p = 0.0161 and p = 0.006, respectively). Finally, cIAP2 knocking down in HPV16 E6/E7 cells resulted in increased apoptosis after exposure to radiation at 4 and 8 Gy (p = 0.0187 and p = 0.0061, respectively). Conclusion This study demonstrated for the first time a positive relationship between HPV presence and cIAP2 levels in OPCs. Additionally, cIAP2 knocking down sensitizes HNC cells to apoptosis promoted by radiation. Therefore, cIAP2 is a potential therapeutic target for radiation in HPV-driven HNC.https://doi.org/10.1186/s13027-024-00609-zCIAP-2Human papillomavirusOropharyngealRadioresistanceCancer |
| spellingShingle | Carolina Oliva Diego Carrillo-Beltrán Julio C. Osorio Iván Gallegos Felipe Carvajal Claudio Mancilla-Miranda Paul Boettiger Enrique Boccardo Francisco Aguayo cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro Infectious Agents and Cancer CIAP-2 Human papillomavirus Oropharyngeal Radioresistance Cancer |
| title | cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro |
| title_full | cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro |
| title_fullStr | cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro |
| title_full_unstemmed | cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro |
| title_short | cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro |
| title_sort | ciap 2 protein is upregulated by human papillomavirus in oropharyngeal cancers role in radioresistance in vitro |
| topic | CIAP-2 Human papillomavirus Oropharyngeal Radioresistance Cancer |
| url | https://doi.org/10.1186/s13027-024-00609-z |
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