Zhu Wenjuan, Yang Qi, Yang Huijun, Qian Mingtao, Ji Yan, Liu Jianyong
Otolaryngology Head and Neck Surgery, Zhangjiagang Hospital Affiliated to Soochow University (Zhang Jiagang First Peoples Hospital), No. 68, West Jiyang Road, Zhangjiagang, 215600, Jiangsu, China.
Discov Oncol. 2025 May 21;16(1):849. doi: 10.1007/s12672-025-02565-5.
Nasopharyngeal carcinoma (NPC) is a highly invasive malignancy with poor prognosis, necessitating further exploration of its molecular mechanisms. While HELLP-associated long non-coding RNA (HELLPAR), microRNA-448 (miR-448), and a disintegrin and metalloprotease 10 (ADAM10) have been implicated in other malignancies, their regulatory interplay and functional roles in NPC remain unclear. This study aimed to investigate the role of HELLPAR in NPC progression through its interaction with miR-448 and ADAM10.
Cancerous and adjacent non-cancerous tissues were collected from 53 NPC patients admitted to our hospital between 1st January 2018 and 1st January 2020. Transcript levels of HELLPAR, miR-448, and ADAM10 were measured using quantitative real-time PCR (RT-qPCR), while the protein expression levels of ADAM10 were assessed by Western blotting. Long-term survival data were analyzed to assess the correlation between HELLPAR expression and patient prognosis. The binding interactions of HELLPAR/miR-448 and miR-448/ADAM10 were predicted and experimentally validated. Overexpression and knockdown constructs for HELLPAR, miR-448, and ADAM10 were transfected into NPC cells to assess their effects on proliferation, invasion, and apoptosis.
HELLPAR and ADAM10 were significantly upregulated at both the RNA and protein levels in NPC tissues and cells, while miR-448 was notably downregulated. Suppression of HELLPAR inhibited NPC cell proliferation and invasion while promoting apoptosis. Mechanistically, HELLPAR functioned as a competitive endogenous RNA (ceRNA) by binding to miR-448, thereby downregulating its RNA expression. Overexpression of miR-448 counteracted the tumor-promoting effects of HELLPAR. Additionally, miR-448 directly targeted and suppressed ADAM10. Overexpression of ADAM10 reversed the inhibitory effects of miR-448 on NPC cell proliferation and invasion.
The HELLPAR/miR-448/ADAM10 axis plays a critical role in NPC progression. Suppressing HELLPAR expression enhances miR-448 activity, which in turn downregulates ADAM10 at both RNA and protein levels, leading to reduced NPC cell proliferation and invasion while promoting apoptosis.
鼻咽癌（NPC）是一种侵袭性很强且预后较差的恶性肿瘤，有必要进一步探究其分子机制。虽然HELLP相关长链非编码RNA（HELLPAR）、微小RNA-448（miR-448）和去整合素金属蛋白酶10（ADAM10）已被证明与其他恶性肿瘤有关，但其在鼻咽癌中的调控相互作用和功能作用仍不清楚。本研究旨在通过HELLPAR与miR-448和ADAM10的相互作用，探讨HELLPAR在鼻咽癌进展中的作用。
收集2018年1月1日至2020年1月1日在我院收治的53例鼻咽癌患者的癌组织及癌旁非癌组织。采用定量实时PCR（RT-qPCR）检测HELLPAR、miR-448和ADAM10的转录水平，同时通过蛋白质印迹法评估ADAM10的蛋白表达水平。分析长期生存数据以评估HELLPAR表达与患者预后之间的相关性。预测并通过实验验证HELLPAR/miR-448和miR-448/ADAM10的结合相互作用。将HELLPAR、miR-448和ADAM10的过表达和敲低构建体转染到鼻咽癌细胞中，以评估它们对细胞增殖、侵袭和凋亡的影响。
HELLPAR和ADAM10在鼻咽癌组织和细胞中的RNA和蛋白质水平均显著上调，而miR-448明显下调。抑制HELLPAR可抑制鼻咽癌细胞增殖和侵袭，并促进细胞凋亡。机制上，HELLPAR作为竞争性内源性RNA（ceRNA）与miR-448结合，从而下调其RNA表达。miR-448的过表达抵消了HELLPAR的促肿瘤作用。此外，miR-448直接靶向并抑制ADAM10。ADAM10的过表达逆转了miR-448对鼻咽癌细胞增殖和侵袭的抑制作用。
HELLPAR/miR-448/ADAM10轴在鼻咽癌进展中起关键作用。抑制HELLPAR表达可增强miR-448活性，进而在RNA和蛋白质水平下调ADAM10，导致鼻咽癌细胞增殖和侵袭减少，同时促进细胞凋亡。
