Cui Yi, Liu Zhihui
The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
Department of Clinical Laboratory, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
PLoS One. 2025 Jun 18;20(6):e0325995. doi: 10.1371/journal.pone.0325995. eCollection 2025.
Lung cancer is the leading cause of cancer-related deaths worldwide, so research and development of potential therapeutic targets is urgent.
The target gene, AKR1C2, was screened using the TCGA and FerrDb databases. The expression of AKR1C2 in lung cancer, its correlation with the clinical characteristics of patients, and the biological roles and molecular mechanisms involved were assessed by bioinformatics. The expression levels of AKR1C2 in normal lung epithelial cells and lung cancer cells were compared by qRT-PCR and Western blot. The effects of AKR1C2 knockdown on the malignant phenotype of lung cancer cells were evaluated using Transwell, wound healing, and CCK8 assays. Finally, the impact of silencing AKR1C2 on malondialdehyde, reactive oxygen species, Fe2+ levels, and ferroptosis-related genes in lung cancer cells were experimentally investigated.
AKR1C2 is highly expressed in lung adenocarcinoma tissues, and the expression level correlates with patient gender, tumor stage, lymph node metastasis, and prognosis. AKR1C2 is associated with substance metabolism, steroid hormone biosynthesis, cellular lipid metabolism, and oxidoreductase activity. AKR1C2 had high expression levels in A549 cells. AKR1C2 silencing inhibited cell viability, invasion, and migration. In A549 cells, AKR1C2 knockdown markedly raised the levels of reactive oxygen species, malondialdehyde, and Fe²⁺. The knockdown of AKR1C2 regulated the expression of ferroptosis-related genes.
Our study demonstrates that AKR1C2 knockdown promotes ferroptosis and inhibits malignant biological behaviors in lung cancer cells.
肺癌是全球癌症相关死亡的主要原因，因此迫切需要研发潜在的治疗靶点。
使用TCGA和FerrDb数据库筛选目标基因AKR1C2。通过生物信息学评估AKR1C2在肺癌中的表达、其与患者临床特征的相关性以及所涉及的生物学作用和分子机制。通过qRT-PCR和蛋白质免疫印迹法比较正常肺上皮细胞和肺癌细胞中AKR1C2的表达水平。使用Transwell、伤口愈合和CCK8实验评估敲低AKR1C2对肺癌细胞恶性表型的影响。最后，通过实验研究沉默AKR1C2对肺癌细胞中丙二醛、活性氧、Fe2+水平和铁死亡相关基因的影响。
AKR1C2在肺腺癌组织中高表达，其表达水平与患者性别、肿瘤分期、淋巴结转移和预后相关。AKR1C2与物质代谢、类固醇激素生物合成、细胞脂质代谢和氧化还原酶活性有关。AKR1C2在A549细胞中表达水平较高。敲低AKR1C2可抑制细胞活力、侵袭和迁移。在A549细胞中，敲低AKR1C2显著提高了活性氧、丙二醛和Fe²⁺的水平。敲低AKR1C2可调节铁死亡相关基因的表达。
我们的研究表明，敲低AKR1C2可促进肺癌细胞的铁死亡并抑制其恶性生物学行为。
