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LncRNA ITGB2-AS1 promotes cisplatin resistance of non-small cell lung cancer by inhibiting ferroptosis via activating the FOSL2/NAMPT axis

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机构: [1]Department of Thoracic Surgery, Yuebei People's Hospital, Shantou University, Shaoguan, Guangdong, People's Republic of China. [2]Department of Pathology, Yuebei People's Hospital, Shantou University, Shaoguan, Guangdong, People's Republic of China. [3]College of Physical Education and Health, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
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关键词: Non-small cell lung cancer cisplatin resistance ferroptosis LncRNA ITGB2- AS1 NAMPT

摘要:
Cisplatin resistance is a major therapeutic challenge in non-small cell lung cancer (NSCLC). Herein, the regulatory role of long non-coding RNA (lncRNA) ITGB2-AS1 in regulating NSCLC cisplatin resistance was investigated. NSCLC cisplatin resistance cells were constructed using A549 and H1975 cells. Cell viability and proliferation were detected by MTT assay and colony formation assay, respectively. Cell apoptosis and cell cycle were examined by flow cytometry. GSH, MDA, ROS, and Fe2+ levels were measured by the corresponding kits. The expressions of ferroptosis-negative regulation genes (GPX4 and SLC7A11) were determined by qRT-PCR and western blot. Molecular interactions were analyzed by RNA pull-down, RIP, ChIP, and dual-luciferase reporter assays. The effects of ITGB2-AS1 silencing on NSCLC cisplatin resistance in vivo were elevated by the tumor xenograft experiment. ITGB2-AS1 expression was increased in NSCLC patients and cisplatin-resistant NSCLC cells, which was positively correlated with ferroptosis-negative regulation genes. ITGB2-AS1 knockdown suppressed resistant cell proliferation and promoted cell apoptosis and ferroptosis. ITGB2-AS1 increased NAMPT expression by binding to FOSL2, thereby repressing p53 expression. The ITGB2-AS1 knockdown also inhibited NSCLC cisplatin resistance in vivo. ITGB2-AS1 promoted NSCLC cisplatin resistance by inhibiting p53-mediated ferroptosis via activating the FOSL2/NAMPT axis.

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出版当年[2022]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 2 区 医学
小类 | 3 区 肿瘤学
第一作者:
第一作者机构: [1]Department of Thoracic Surgery, Yuebei People's Hospital, Shantou University, Shaoguan, Guangdong, People's Republic of China. [*1]Department of Thoracic Surgery, Yuebei People’s Hospital, Shantou University, No.133 Huimin South Road, Wujiang District, Shaoguan 512026, People’s Republic of China
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通讯机构: [1]Department of Thoracic Surgery, Yuebei People's Hospital, Shantou University, Shaoguan, Guangdong, People's Republic of China. [*1]Department of Thoracic Surgery, Yuebei People’s Hospital, Shantou University, No.133 Huimin South Road, Wujiang District, Shaoguan 512026, People’s Republic of China
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