[1]韩鹏,杨艺员,王源波,等.NDUFA4L2通过抑制缺氧条件下活性氧生成促进肺鳞癌进展的研究[J].陕西医学杂志,2025,54(7):867-872.[doi:DOI:10.3969/j.issn.1000-7377.2025.07.001]
　HAN Peng,YANG Yiyuan,WANG Yuanbo,et al.NDUFA4L2 promotes lung squamous cell carcinoma progression by inhibiting ROS generation under hypoxia[J].,2025,54(7):867-872.[doi:DOI:10.3969/j.issn.1000-7377.2025.07.001]
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NDUFA4L2通过抑制缺氧条件下活性氧生成促进肺鳞癌进展的研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年7期
页码:
867-872
栏目:
基础研究
出版日期:
2025-07-05

文章信息/Info

Title:
NDUFA4L2 promotes lung squamous cell carcinoma progression by inhibiting ROS generation under hypoxia
作者:
韩鹏1; 2; 杨艺员1; 王源波1; 周洁君3; 刘岩1; 梁一倩1
（1.西安交通大学第一附属医院核医学科，陕西 西安710061；2.西安交通大学第一附属医院耳鼻咽喉头颈外科，陕西 西安710061；3.西安交通大学第一附属医院呼吸与危重症医学科，陕西 西安710061）
Author(s):
HAN Peng1; 2; YANG Yiyuan1; WANG Yuanbo1; ZHOU Jiejun3; LIU Yan1; LIANG Yiqian1
（1.Department of Nuclear Medicine，The First Affiliated Hospital of Xi’an Jiaotong University，Xi’an 710061，China；2.Department of Otolaryngology-Head and Neck Surgery，The First Affiliated Hospital of Xi’an Jiaotong University，Xi’an 710061，China；3.Department of Respiratory and Critical Care Medicine，The First Affiliated Hospital of Xi’an Jiaotong University，Xi’an 710061，China）
关键词:
肺鳞癌; NDUFA4L2; 缺氧诱导因子-1; 缺氧; 活性氧; 细胞增殖
Keywords:
Lung squamous cell carcinoma; NDUFA4L2; HIF-1α; Hypoxia; Reactive oxygen species; Cell proliferation
分类号:
R 734.2
DOI:
DOI:10.3969/j.issn.1000-7377.2025.07.001
文献标志码:
A
摘要:
目的：探究缺氧条件下肺鳞癌细胞NDUFA4L2的表达情况和对细胞增殖、凋亡的影响及其分子机制，为肺鳞癌靶向治疗提供新的靶点。方法：缺氧或常氧培养人肺鳞癌细胞系NCI-H226，Western blot法检测NDUFA4L2表达以及小干扰RNA（siRNA）敲减缺氧诱导因子-1（HIF-1α）对NDUFA4L2表达的影响；应用超氧化物阴离子荧光探针检测缺氧条件下细胞内活性氧（ROS）水平。构建NDUFA4L2敲减（NCI-H226-shNDUFA4L2）及对照组（NCI-H226-shControl）细胞模型，采用CCK-8法及流式细胞术检测NDUFA4L2敲减及抗氧化剂（NAC）对肺鳞癌细胞增殖、凋亡及细胞周期的作用。结果：缺氧培养NCI-H226细胞的NDUFA4L2表达水平较常氧培养显著增加（P=0.019）。应用siRNA敲减HIF-1α可显著抑制缺氧条件下NDUFA4L2的表达（P＜0.001）。与NCI-H226-shControl细胞相比，缺氧条件下NCI-H226-shNDUFA4L2细胞的ROS水平显著增高（P＜0.001）；NAC可明显降低NDUFA4L2敲减引起的细胞内ROS水平增高（P＜0.001）。与NCI-H226-shControl细胞相比，缺氧条件下NCI-H226-shNDUFA4L2细胞的增殖能力显著降低，凋亡率显著增加，细胞周期G1期细胞比率升高，S期细胞比例下调（均P＜0.001）。NAC可逆转NDUFA4L2敲减对NCI-H226增殖、凋亡和细胞周期的影响（均P＜0.001）。结论：缺氧通过HIF-1α介导NDUFA4L2表达上调，NDUFA4L2可能通过抑制缺氧时肺鳞癌细胞内ROS的生成发挥促进肿瘤进展的作用。
Abstract:
Objective:To investigate the expression of NDUFA4L2 in lung squamous cell carcinoma(LUSC) cells under hypoxic conditions，as well as its effects on cell proliferation，apoptosis，and the underlying molecular mechanisms.Methods：Human LUSC cell line NCI-H226 was cultured under hypoxic or normoxic conditions.The expression of NDUFA4L2 and the effect of HIF-1α knockdown via siRNA on NDUFA4L2 expression were detected by Western blot.The levels of reactive oxygen species(ROS) in cells under hypoxic conditions were measured using a superoxide anion fluorescent probe.NDUFA4L2 knockdown(NCI-H226-shNDUFA4L2) and control(NCI-H226-shControl) cell models were constructed，and the effects of NDUFA4L2 knockdown and antioxidant NAC on cell proliferation，apoptosis，and cell cycle were detected by CCK-8 assay and flow cytometry.Results:The expression level of NDUFA4L2 in NCI-H226 cells cultured under hypoxia was significantly increased compared with that under normoxia(P=0.019).Knockdown of HIF-1α by siRNA significantly inhibited the expression of NDUFA4L2 under hypoxic conditions(P＜0.001).Compared with NCI-H226-shControl cells，ROS levels in NCI-H226-shNDUFA4L2 cells under hypoxic conditions were significantly increased(P＜0.001)；ROS induced by NDUFA4L2 knockdown was significantly rescued by NAC treatment(P＜0.001).Compared with NCI-H226-shControl cells，NCI-H226-shNDUFA4L2 cells under hypoxic conditions showed significantly reduced proliferation，increased apoptosis，an increased proportion of cells in the G1 phase，and a decreased proportion of cells in the S phase(all P＜0.001).NAC reversed the effects of NDUFA4L2 knockdown on NCI-H226 proliferation，apoptosis，and cell cycle(all P＜0.001).Conclusion:Hypoxia induces the upregulation of NDUFA4L2 expression through HIF-1α，and NDUFA4L2 may promote tumor progression by inhibiting the generation of ROS in LUSC cells under hypoxic conditions.

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备注/Memo

备注/Memo:
国家自然科学基金资助青年项目（81902322）；陕西省自然科学基础研究计划项目（2020JQ-526、2023-JC-YB-791）；西安交通大学第一附属医院院基金资助项目（2021ZYTS-02）
更新日期/Last Update: 2025-07-07