Krishnan Aswini R, Qu Yuanhao, Li Pin Xue, Zou Angela E, Califano Joseph A, Wang-Rodriguez Jessica, Ongkeko Weg M
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, USA.
Veterans Administration San Diego Healthcare System and Department of Pathology, University of California San Diego, La Jolla, California, USA.
Oncotarget. 2017 Dec 19;9(4):4614-4624. doi: 10.18632/oncotarget.23464. eCollection 2018 Jan 12.
Human papillomavirus (HPV) infection is the fastest growing cause of head and neck squamous cell carcinoma (HNSCC) today, but its role in malignant transformation remains unclear. This study aimed to conduct a comprehensive investigation of PIWI-interacting RNA (piRNA) alterations and functionalities in HPV-induced HNSCC. Using 77 RNA-sequencing datasets from TCGA, we examined differential expression of piRNAs between HPV16(+) HNSCC and HPV(-) Normal samples, identifying a panel of 30 HPV-dysregulated piRNAs. We then computationally investigated the potential mechanistic significances of these transcripts in HPV-induced HNSCC, identifying our panel of piRNAs to associate with the protein PIWIL4 as well as the RTL family of retrotransposon-like genes, possibly through direct binding interactions. We also recognized several HPV-dysregulated transcripts for their correlations with well-documented mutations and copy number variations in HNSCC as well as HNSCC clinical variables, demonstrating the potential ability of our piRNAs to play important roles in large-scale modulation of HNSCC in addition to their direct, smaller-scale interactions in this malignancy. The differential expression of key piRNAs, including , , and , was verified by evaluating endogenous expression in HPV(+) cancer vs. HPV(-) normal cell lines. Overall, our novel study provides a rigorous investigation of piRNA dysregulation in HPV-related HNSCC, and lends critical insight into the idea that these small regulatory transcripts may play crucial and previously unidentified roles in tumor pathogenesis and progression.
人乳头瘤病毒（HPV）感染是当今头颈部鳞状细胞癌（HNSCC）增长最快的病因，但其在恶性转化中的作用仍不清楚。本研究旨在全面调查PIWI相互作用RNA（piRNA）在HPV诱导的HNSCC中的改变和功能。利用来自TCGA的77个RNA测序数据集，我们检测了HPV16（+）HNSCC和HPV（-）正常样本之间piRNA的差异表达，鉴定出一组30个HPV失调的piRNA。然后，我们通过计算研究了这些转录本在HPV诱导的HNSCC中的潜在机制意义，确定我们的piRNA组可能通过直接结合相互作用与PIWIL4蛋白以及逆转录转座子样基因的RTL家族相关联。我们还认识到一些HPV失调的转录本与HNSCC中记录良好的突变、拷贝数变异以及HNSCC临床变量之间的相关性，这表明我们的piRNA除了在这种恶性肿瘤中具有直接的、较小规模的相互作用外，还具有在HNSCC大规模调节中发挥重要作用的潜在能力。通过评估HPV（+）癌细胞与HPV（-）正常细胞系中的内源性表达，验证了关键piRNA（包括……和……）的差异表达。总体而言，我们的新研究对HPV相关HNSCC中piRNA失调进行了严谨的调查，并为这些小调节转录本可能在肿瘤发病机制和进展中发挥关键且先前未被识别的作用这一观点提供了重要见解。
