环状RNA circ_0015278通过miR-1228/P53轴诱导肺腺癌中的铁死亡。
CircRNA circ_0015278 induces ferroptosis in lung adenocarcinoma through the miR-1228/P53 axis.
作者信息
Xia Liangjiang, Li Guangbin, Zhou Qingwu, Feng Y U, Ma Haitao
机构信息
Department of Thoracic Surgery, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
出版信息
Oncol Res. 2025 Jan 16;33(2):465-475. doi: 10.32604/or.2024.050835. eCollection 2025.
BACKGROUND
Circular RNAs play an important role in regulating lung adenocarcinoma (LUAD). Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD. However, the biological mechanism of circ_0015278 in LUAD has not been fully clarified, especially in ferroptosis.
MATERIALS AND METHODS
Bioinformatics analysis was employed to explore the downstream mechanisms of Circ_0015278, subsequently confirmed by luciferase reporter assays. The impact of Circ_0015278 on cell proliferation, migration, invasion, and ferroptosis was investigated through a loss-of-function experiment. A xenotransplantation mouse model elucidated the effect of Circ_0015278 on tumour growth.
RESULTS
Circ_0015278 exhibited downregulation in LUAD. It inhibited cell proliferation, migration, and invasion while promoting ferroptosis by interacting with miR-1228 to regulate P53 expression through a competitive endogenous RNA mechanism. Moreover, circ_0015278 suppressed tumour growth in mice.
CONCLUSIONS
Circ_0015278 was identified as a novel factor promoting ferroptosis in LUAD. Furthermore, it suppressed the malignant progression of LUAD through the miR-1228/P53 axis.
背景
环状RNA在调节肺腺癌（LUAD）中起重要作用。生物信息学分析确定circ_0015278在LUAD中差异表达。然而，circ_0015278在LUAD中的生物学机制尚未完全阐明，尤其是在铁死亡方面。
材料与方法
采用生物信息学分析探索Circ_0015278的下游机制，随后通过荧光素酶报告基因检测进行验证。通过功能缺失实验研究Circ_0015278对细胞增殖、迁移、侵袭和铁死亡的影响。异种移植小鼠模型阐明了Circ_0015278对肿瘤生长的影响。
结果
Circ_0015278在LUAD中表达下调。它通过与miR-1228相互作用，以竞争性内源RNA机制调节P53表达，从而抑制细胞增殖、迁移和侵袭，同时促进铁死亡。此外，circ_0015278抑制小鼠肿瘤生长。
结论
Circ_0015278被确定为促进LUAD铁死亡的新因子。此外，它通过miR-1228/P53轴抑制LUAD的恶性进展。
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