Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Radiotherapy, Guangxi Medical University Cancer Hospital, Nanning, China.
FEBS Open Bio. 2023 Jan;13(1):102-117. doi: 10.1002/2211-5463.13519. Epub 2022 Nov 28.
Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA-binding protein WD repeat and HMG-box DNA-binding protein 1 (WDHD1) are highly expressed in a variety of tumours, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non-NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP-seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to the cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have the potential as a target gene for primary screening and treatment of NPC.
鼻咽癌（NPC）是一种高度转移性和侵袭性的恶性肿瘤，起源于鼻咽部。DNA 结合蛋白 WD 重复和 HMG 盒 DNA 结合蛋白 1（WDHD1）在多种肿瘤中高表达，但迄今为止尚未报道其在 NPC 中的表达及其作用机制。为了研究 WDHD1 在 NPC 中的作用，我们首先从数据库中挖掘 NPC 的基因表达谱。对 338 例 NPC 和 112 例非 NPC 样本进行免疫组织化学（IHC）验证。我们报告 WDHD1 在 NPC 中表达明显上调。ChIP-seq 显示整合素 alpha V（ITGAV）和 WDHD1 在 ITGAV 基因启动子区域表现出显著的结合峰。ITGAV 和 WDHD1 的表达水平呈显著正相关，IHC 显示 ITGAV 在 NPC 中高表达。过表达 WDHD1 后 ITGAV 的表达增加，表明 ITGAV 可能是 WDHD1 的潜在靶基因。通路分析表明，两个基因都与细胞周期密切相关，流式细胞术进一步证实，WDHD1 的表达降低显著增加了凋亡细胞的数量。总之，我们的结果表明，WDHD1 在 NPC 中表达增加，可能与 NPC 细胞周期有关；因此，我们提出 WDHD1 可能具有作为 NPC 初筛和治疗的靶基因的潜力。
