Department of Dentistry, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Brazil.
Federal University of Alagoas (UFAL), Arapiraca, Alagoas, Brazil.
J Oral Pathol Med. 2021 Nov;50(10):985-994. doi: 10.1111/jop.13188. Epub 2021 May 24.
Head and neck squamous cell carcinoma (HNSC) etiopathogenesis remains unclear, and the biological changes with the activation of heat shock proteins (HSPs) and prion protein (PRNP) promoted by hypoxia in HNSC are undetermined. This study investigates hypoxia's effect in lymph node metastasis by PRNP expression changes and its main partners.
The study combined a theoretical/cell culture study with a case-control study. First, bioinformatics and cell culture were performed. A case-control study was performed in a second step by comparing HNSC patients with and without lymph node metastasis.
The Cancer Genome Atlas (TCGA) data source validates the theory in the global population study.
Bioinformatics analysis suggests that hypoxia-inducible factor-1α (HIF1A) is associated with HSPA4, HSP90AA1 and PRNP expression. TCGA data validate the hypothesis that higher HSP90AA1, HSPA4 and PRNP are related to metastases and low survival. Herein, the cell study demonstrated that muted PRNP did not respond to hypoxia.
Our results collectively provide the first evidence that PRNP promotes HNSC lymph node metastasis progression through the upregulation of HSPA4, HSP90AA1 and HIF1A. Our findings may provide a molecular basis for the promoting Role of PRNP in HNSC progression.
头颈部鳞状细胞癌（HNSC）的病因仍然不清楚，并且 HNSC 中由缺氧引起的热休克蛋白（HSPs）和朊病毒蛋白（PRNP）的激活所导致的生物学变化尚不确定。本研究通过 PRNP 表达变化及其主要伙伴研究了缺氧对淋巴结转移的影响。
该研究将理论/细胞培养研究与病例对照研究相结合。首先进行了生物信息学和细胞培养，其次在第二步通过比较有和无淋巴结转移的 HNSC 患者进行了病例对照研究。
癌症基因组图谱（TCGA）数据源验证了全球人群研究中的理论。
生物信息学分析表明，缺氧诱导因子-1α（HIF1A）与 HSPA4、HSP90AA1 和 PRNP 的表达相关。TCGA 数据验证了较高的 HSP90AA1、HSPA4 和 PRNP 与转移和低生存率相关的假设。在此，细胞研究表明，沉默的 PRNP 对缺氧没有反应。
我们的研究结果首次提供了证据，证明 PRNP 通过上调 HSPA4、HSP90AA1 和 HIF1A 促进 HNSC 淋巴结转移进展。我们的发现可能为 PRNP 在 HNSC 进展中的促进作用提供了分子基础。
