LncRNA HNF1A-AS1通过miR-124/ PKM2轴抑制口腔鳞状细胞癌细胞铁下垂。

IF 2 3区医学 Q2 Dentistry

Journal of Stomatology Oral and Maxillofacial Surgery Pub Date : 2025-08-12 DOI:10.1016/j.jormas.2025.102522

Lu Deng, Qiang Tang, Huiqin Lv, Zhe Liu

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引用次数: 0

摘要

目的：本研究旨在阐明lncRNA HNF1A-AS1在OSCC铁下垂中的分子机制，为OSCC的治疗提供新的治疗意义。方法：采用人OSCC细胞系CAL-27、SCC-15、HSC-3、WSU-HN12和正常人口腔角质形成细胞（NHOK）进行体外实验。通过检测细胞增殖、基因表达、蛋白表达水平及凋亡相关指标，评估lncRNA HNF1A-AS1对OSCC铁下垂的作用。通过双荧光素酶报告基因测定和RIP测定验证了miR-124与HNF1A-AS1之间以及miR-124与PKM2的3'UTR之间的结合关系。将miR-124抑制或PKM2过表达与沉默HNF1A-AS1结合进行功能验证。统计学分析比较不同处理间各项指标的变化。结果：在OSCC细胞中，HNF1A-AS1和PKM2过表达，miR-124表达下调。沉默HNF1A-AS1抑制细胞增殖，提高ROS、MDA和Fe2+含量，降低GSH含量，增强ACSL4表达，降低GPX4表达。在机制上，HNF1A-AS1结合并隔离miR-124的表达，miR-124结合并抑制PKM2的表达。miR-124抑制和PKM2过表达都部分逆转了HNF1A-AS1沉默对OSCC细胞铁下垂的促进作用。结论：HNF1A-AS1通过结合miR-124抑制OSCC细胞铁下垂，减轻PKM2的转录抑制。我们的研究为OSCC的治疗提供了一个潜在的治疗策略。

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LncRNA HNF1A-AS1 inhibits ferroptosis in oral squamous cell carcinoma cells through the miR-124/ PKM2 axis.

Objectives: The aim of this study was to illustrate the molecular mechanism of lncRNA HNF1A-AS1 in ferroptosis in OSCC, providing novel therapeutic implications for OSCC treatment.

Methods: Human OSCC cell lines (CAL-27, SCC-15, HSC-3, WSU-HN12) and normal human oral keratinocytes (NHOK) were used for in vitro experiments. The function of lncRNA HNF1A-AS1 on ferroptosis in OSCC was evaluated through measurement of cell proliferation, gene expression, protein expression levels, and ferroptosis-related indicators. The binding relationships between miR-124 and HNF1A-AS1, as well as between miR-124 and the 3'UTR of PKM2, were verified using dual-luciferase reporter gene assays and RIP assays. miR-124 inhibition or PKM2 overexpression was combined with silencing of HNF1A-AS1 for functional verification. Statistical analysis was performed to compare changes in the indicators among different treatments.

Results: In OSCC cells, HNF1A-AS1 and PKM2 were overexpressed, while miR-124 expression was downregulated. Silencing HNF1A-AS1 suppressed cell proliferation, elevated contents of ROS, MDA and Fe²⁺, reduced GSH content, enhanced ACSL4 expression and diminished GPX4 expression. Mechanistically, HNF1A-AS1 bound to and sequestered miR-124, and miR-124 bound to and inhibited PKM2 expression. Both miR-124 inhibition and PKM2 overexpression partially reversed the promotive effect of HNF1A-AS1 silencing on OSCC cell ferroptosis.

Conclusion: HNF1A-AS1 inhibits OSCC cell ferroptosis by binding to miR-124 to relieve the transcriptional inhibition of PKM2. Our study offers a potential therapeutic strategy for OSCC treatment.

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来源期刊

Journal of Stomatology Oral and Maxillofacial Surgery Dentistry-Oral Surgery

CiteScore

2.20

自引率

9.10%

发文量

305

期刊介绍： J Stomatol Oral Maxillofac Surg publishes research papers and techniques - (guest) editorials, original articles, reviews, technical notes, case reports, images, letters to the editor, guidelines - dedicated to enhancing surgical expertise in all fields relevant to oral and maxillofacial surgery: from plastic and reconstructive surgery of the face, oral surgery and medicine, … to dentofacial and maxillofacial orthopedics. Original articles include clinical or laboratory investigations and clinical or equipment reports. Reviews include narrative reviews, systematic reviews and meta-analyses. All manuscripts submitted to the journal are subjected to peer review by international experts, and must: Be written in excellent English, clear and easy to understand, precise and concise; Bring new, interesting, valid information - and improve clinical care or guide future research; Be solely the work of the author(s) stated; Not have been previously published elsewhere and not be under consideration by another journal; Be in accordance with the journal''s Guide for Authors'' instructions: manuscripts that fail to comply with these rules may be returned to the authors without being reviewed. Under no circumstances does the journal guarantee publication before the editorial board makes its final decision. The journal is indexed in the main international databases and is accessible worldwide through the ScienceDirect and ClinicalKey Platforms.