Carolina Oliva, Diego Carrillo-Beltrán, Julio C Osorio, Iván Gallegos, Felipe Carvajal, Claudio Mancilla-Miranda, Paul Boettiger, Enrique Boccardo, Francisco Aguayo
{"title":"人乳头瘤病毒在口咽癌中上调cIAP-2蛋白：在体外放射抗性中的作用。","authors":"Carolina Oliva, Diego Carrillo-Beltrán, Julio C Osorio, Iván Gallegos, Felipe Carvajal, Claudio Mancilla-Miranda, Paul Boettiger, Enrique Boccardo, Francisco Aguayo","doi":"10.1186/s13027-024-00609-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"47"},"PeriodicalIF":3.1000,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429157/pdf/","citationCount":"0","resultStr":"{\"title\":\"cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro.\",\"authors\":\"Carolina Oliva, Diego Carrillo-Beltrán, Julio C Osorio, Iván Gallegos, Felipe Carvajal, Claudio Mancilla-Miranda, Paul Boettiger, Enrique Boccardo, Francisco Aguayo\",\"doi\":\"10.1186/s13027-024-00609-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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. 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cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro.
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.
期刊介绍：
Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer.
The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular:
• HPV and anogenital cancers, as well as head and neck cancers;
• EBV and Burkitt lymphoma;
• HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases;
• HHV8 and Kaposi sarcoma;
• HTLV and leukemia;
• Cancers in Low- and Middle-income countries.
The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries.
Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.
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