Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC
Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) encompasses a heterogeneous group of malignancies characterized by diverse clinical manifestations. Notably, HPV-positive HNSCC exhibits a more favorable prognosis, particularly when the virus is transcriptionally acti...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924001681 |
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| author | Nikita Aggarwal Divya Janjua Apoorva Chaudhary Udit Joshi Tanya Tripathi Chetkar Chandra Keshavam Joni Yadav Arun Chhokar Alok Chandra Bharti |
| author_facet | Nikita Aggarwal Divya Janjua Apoorva Chaudhary Udit Joshi Tanya Tripathi Chetkar Chandra Keshavam Joni Yadav Arun Chhokar Alok Chandra Bharti |
| author_sort | Nikita Aggarwal |
| collection | DOAJ |
| description | Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) encompasses a heterogeneous group of malignancies characterized by diverse clinical manifestations. Notably, HPV-positive HNSCC exhibits a more favorable prognosis, particularly when the virus is transcriptionally active. This study aimed to elucidate the role of key transcription factors in activating the HPV long control region (LCR), responsible for its oncogenic potential. Utilizing immunoblotting and immunofluorescence techniques, we analyzed the expression and nuclear localization of LCR-associated transcription factors in HPV-negative and HPV-positive HNSCC cell lines. High expression of JunB and low expression of Fra-1, pSTAT3(S727), SP1, and SOX2 were observed in HPV-positive HNSCC cells. Transcriptomic analysis corroborated these findings, revealing differential expression of transcription factors in HPV-positive lesions. Moreover, the study identified strong correlation of LCR-specific transcription factors with HNSCC patient survival. Evaluation of HPV16 LCR reporter activity further underscored the heterogeneous nature of HNSCC, with some HPV-negative cell lines exhibiting comparable LCR activity to HPV-positive counterparts. These findings elucidate the intricate regulatory mechanisms underlying HPV-associated HNSCC and provide insights into potential prognostic markers and therapeutic targets. |
| format | Article |
| id | doaj-art-8911c6dc36364c438d401a558317e346 |
| institution | Kabale University |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-8911c6dc36364c438d401a558317e3462025-01-14T04:12:43ZengElsevierMolecular Therapy: Oncology2950-32992025-03-01331200926Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCCNikita Aggarwal0Divya Janjua1Apoorva Chaudhary2Udit Joshi3Tanya Tripathi4Chetkar Chandra Keshavam5Joni Yadav6Arun Chhokar7Alok Chandra Bharti8Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, IndiaMolecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, IndiaMolecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, IndiaMolecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, IndiaMolecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, IndiaMolecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, IndiaMolecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, IndiaMolecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India; Department of Zoology, Deshbandu College, University of Delhi, Delhi, IndiaMolecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India; Corresponding author: Alok Chandra Bharti, Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi 110007, IndiaHuman papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) encompasses a heterogeneous group of malignancies characterized by diverse clinical manifestations. Notably, HPV-positive HNSCC exhibits a more favorable prognosis, particularly when the virus is transcriptionally active. This study aimed to elucidate the role of key transcription factors in activating the HPV long control region (LCR), responsible for its oncogenic potential. Utilizing immunoblotting and immunofluorescence techniques, we analyzed the expression and nuclear localization of LCR-associated transcription factors in HPV-negative and HPV-positive HNSCC cell lines. High expression of JunB and low expression of Fra-1, pSTAT3(S727), SP1, and SOX2 were observed in HPV-positive HNSCC cells. Transcriptomic analysis corroborated these findings, revealing differential expression of transcription factors in HPV-positive lesions. Moreover, the study identified strong correlation of LCR-specific transcription factors with HNSCC patient survival. Evaluation of HPV16 LCR reporter activity further underscored the heterogeneous nature of HNSCC, with some HPV-negative cell lines exhibiting comparable LCR activity to HPV-positive counterparts. These findings elucidate the intricate regulatory mechanisms underlying HPV-associated HNSCC and provide insights into potential prognostic markers and therapeutic targets.http://www.sciencedirect.com/science/article/pii/S2950329924001681MT: Regular Issuehuman papillomavirus, HPVhead and neck squamous cell carcinoma, HNSCClong control region, LCRtranscription factorsexpression |
| spellingShingle | Nikita Aggarwal Divya Janjua Apoorva Chaudhary Udit Joshi Tanya Tripathi Chetkar Chandra Keshavam Joni Yadav Arun Chhokar Alok Chandra Bharti Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC Molecular Therapy: Oncology MT: Regular Issue human papillomavirus, HPV head and neck squamous cell carcinoma, HNSCC long control region, LCR transcription factors expression |
| title | Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC |
| title_full | Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC |
| title_fullStr | Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC |
| title_full_unstemmed | Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC |
| title_short | Insights into expression and localization of HPV16 LCR-associated transcription factors and association with LCR activity in HNSCC |
| title_sort | insights into expression and localization of hpv16 lcr associated transcription factors and association with lcr activity in hnscc |
| topic | MT: Regular Issue human papillomavirus, HPV head and neck squamous cell carcinoma, HNSCC long control region, LCR transcription factors expression |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924001681 |
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