Department of Gastroenterology, First Affiliated Hospital of Gannan Medical University, Ganzhou City, China.
Department of Clinical Laboratory, First Affiliated Hospital of Gannan Medical University, Ganzhou City, China.
J Biochem Mol Toxicol. 2024 Aug;38(8):e23771. doi: 10.1002/jbt.23771.
Colon cancer contributes to high mortality rates internationally that has seriously endangered human health. Aurora kinase A (AURKA) served as a key molecule in colon cancer. However, its role of AURKA on regulating ferroptosis in colon cancer and their possible interactions with miRNAs and circRNAs remain still elusive. Comprehensive bioinformatics analysis after RNA-sequencing was conducted to determine the differentially expressed genes (DEGs), ferroptosis-related DEGs and hub genes. The direct relationship between miR-506-3p and hsa_circRNA_007630 or AURKA was predicted, then verified by dual luciferase reporter and quantitative real-time polymerase chain reaction. The rescue experiments were conducted by cotransfection with si-hsa_circRNA_007630, miR-506-3p inhibitor or pcDNA-AURKA in HT29 cells. Erastin was used to induce ferroptosis in HT29 cells and validated by detecting levels of intracellular Fe, lipid reactive oxygen species, glutathione, malondialdehyde and ferroptosis markers expression. We screened a total of 331 DEGs, 26 ferroptosis-related genes, among which 3 hub genes were identified through PPI network analysis. Therein, AURKA expression was elevated in colon cancer cells. Moreover, AURKA was targeted by miR-506-3p, and hsa_circRNA_007630 operated as miR-506-3p sponge. The effect of hsa_circRNA_007630 depletion on the inhibiting malignant phenotypes of HT29 cells was rescued by inhibition of miR-506-3p or AURKA overexpression. Additionally, AURKA reduced erastin-induced ferroptosis in HT29 cells. Depletion of circRNA_007630 exerts as a suppressive role in colon cancer through a novel miR-506-3p/AURKA pathway related to ferroptosis, and might become a novel marker for colon cancer.
结肠癌在国际上导致高死亡率，严重威胁人类健康。极光激酶 A（AURKA）是结肠癌的关键分子。然而，AURKA 在调节结肠癌中铁死亡的作用及其与 miRNAs 和 circRNAs 的可能相互作用仍然难以捉摸。通过 RNA-seq 进行综合生物信息学分析，确定差异表达基因（DEGs）、铁死亡相关 DEGs 和枢纽基因。预测 miR-506-3p 与 hsa_circRNA_007630 或 AURKA 之间的直接关系，然后通过双荧光素酶报告和实时定量聚合酶链反应验证。在 HT29 细胞中转染 si-hsa_circRNA_007630、miR-506-3p 抑制剂或 pcDNA-AURKA 进行挽救实验。用 erastin 诱导 HT29 细胞铁死亡，并通过检测细胞内 Fe、脂质活性氧、谷胱甘肽、丙二醛和铁死亡标志物表达水平进行验证。我们筛选了总共 331 个 DEGs 和 26 个铁死亡相关基因，通过 PPI 网络分析鉴定了 3 个枢纽基因。其中，AURKA 在结肠癌细胞中表达上调。此外，AURKA 是 miR-506-3p 的靶基因，hsa_circRNA_007630 作为 miR-506-3p 的海绵。抑制 miR-506-3p 或过表达 AURKA 可挽救 hsa_circRNA_007630 耗竭对 HT29 细胞恶性表型的抑制作用。此外，AURKA 降低了 erastin 诱导的 HT29 细胞铁死亡。circRNA_007630 的缺失通过与铁死亡相关的新型 miR-506-3p/AURKA 通路在结肠癌中发挥抑制作用，并可能成为结肠癌的新标志物。
