Aggarwal Nikita, Janjua Divya, Chaudhary Apoorva, Joshi Udit, Tripathi Tanya, Chandra Keshavam Chetkar, Yadav Joni, Chhokar Arun, Chandra Bharti Alok
Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India.
Department of Zoology, Deshbandu College, University of Delhi, Delhi, India.
Mol Ther Oncol. 2024 Dec 21;33(1):200926. doi: 10.1016/j.omton.2024.200926. eCollection 2025 Mar 20.
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.
人乳头瘤病毒（HPV）阳性的头颈部鳞状细胞癌（HNSCC）是一组异质性恶性肿瘤，具有多种临床表现。值得注意的是，HPV阳性的HNSCC预后较好，尤其是当病毒处于转录活跃状态时。本研究旨在阐明关键转录因子在激活HPV长控制区（LCR）中的作用，LCR对其致癌潜能起关键作用。利用免疫印迹和免疫荧光技术，我们分析了HPV阴性和HPV阳性HNSCC细胞系中LCR相关转录因子的表达和核定位。在HPV阳性的HNSCC细胞中观察到JunB高表达，而Fra-1、pSTAT3（S727）、SP1和SOX2低表达。转录组分析证实了这些发现，揭示了HPV阳性病变中转录因子的差异表达。此外，该研究确定了LCR特异性转录因子与HNSCC患者生存率之间的强相关性。对HPV16 LCR报告基因活性的评估进一步强调了HNSCC的异质性，一些HPV阴性细胞系表现出与HPV阳性细胞系相当的LCR活性。这些发现阐明了HPV相关HNSCC潜在的复杂调控机制，并为潜在的预后标志物和治疗靶点提供了见解。
