Chen Jia, Deng Xiaoyu, Xie Hansheng, Wang Caiyun, Huang Jiefeng, Lian Ningfang
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
Fujian Provincial Sleep-Disordered Breathing Clinic Center, Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2024 Feb 3;19:363-374. doi: 10.2147/COPD.S444402. eCollection 2024.
Circular RNA (circRNA) plays an important role in various biological processes. However, their functions in cigarette smoke extract (CSE) induced human normal lung epithelial cells (BEAS-2B) injury remain vague. The study aimed to explore circRNA expression profiles and reveal their potential roles in CSE-treated BEAS-2B cells.
5% CSE exposure for 24 hours were used to build the BEAS-2B cells ferroptosis model. Differentially expressed circRNAs (DECs) were identified by next-generation RNA sequencing. Six randomly selected DECs were validated via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis were conducted to clarify the potential functions of the DECs. Furthermore, the role of hsa_circ_0025843 in CSE-related BEAS-2B cells ferroptosis was confirmed.
5% CSE exposure induced BEAS-2B cells ferroptosis. Fifty-one up-regulated cirRNAs and 80 down-regulated circRNAs were revealed in CSE-treated BEAS-2B cells. Hsa_circ_0003461, hsa_circ_0007548, hsa_circ_0025843, hsa_circ_0068896, hsa_circ_0005832, and hsa_circ_0053378 were selected randomly to validate the reliability of next-generation RNA sequencing by qRT-PCR. After KEGG pathway analysis, DECs were found to participate in the process of EGFR tyrosine kinase inhibitor resistance and glycerophospholipid metabolism. The knockdown of hsa_circ_0025843 significantly alleviated CSE-induced BEAS-2B cells ferroptosis.
The study indicated the circRNA expression profiles in CSE-treated BEAS-2B cells. Hsa_circ_0025843 alleviated CSE induced BEAS-2B cells ferroptosis, which might be a potential therapeutic target of CSE related lung injury.
环状RNA（circRNA）在多种生物学过程中发挥重要作用。然而，它们在香烟烟雾提取物（CSE）诱导的人正常肺上皮细胞（BEAS-2B）损伤中的功能仍不明确。本研究旨在探索circRNA表达谱，并揭示其在CSE处理的BEAS-2B细胞中的潜在作用。
采用5% CSE处理24小时构建BEAS-2B细胞铁死亡模型。通过下一代RNA测序鉴定差异表达的circRNA（DECs）。通过定量逆转录聚合酶链反应（qRT-PCR）验证随机选择的6个DECs。进行京都基因与基因组百科全书（KEGG）通路分析和基因本体论（GO）分析以阐明DECs的潜在功能。此外，证实了hsa_circ_0025843在CSE相关的BEAS-2B细胞铁死亡中的作用。
5% CSE处理诱导BEAS-2B细胞铁死亡。在CSE处理的BEAS-2B细胞中发现51个上调的circRNA和80个下调的circRNA。随机选择hsa_circ_0003461、hsa_circ_0007548、hsa_circ_0025843、hsa_circ_0068896、hsa_circ_0005832和hsa_circ_0053378通过qRT-PCR验证下一代RNA测序的可靠性。KEGG通路分析后，发现DECs参与表皮生长因子受体酪氨酸激酶抑制剂抗性和甘油磷脂代谢过程。敲低hsa_circ_0025843可显著减轻CSE诱导的BEAS-2B细胞铁死亡。
本研究表明了CSE处理的BEAS-2B细胞中的circRNA表达谱。hsa_circ_0025843减轻了CSE诱导的BEAS-2B细胞铁死亡，这可能是CSE相关肺损伤的潜在治疗靶点。
