环状RNA KIF4A在结直肠癌中表达与功能及其作用机制

背景与目的：环状RNA KIF4A (circKIF4A)被发现在多种肿瘤的恶性进展中起到重要作用，然而，circKIF4A在结直肠癌中的生物学作用尚未见报道。因此，本研究探讨circKIF4A对结直肠癌生物学行为的影响及机制。方法：用qRT-PCR检测不同结直肠癌细胞系与结肠黏膜上皮细胞以及结直肠癌组织与癌旁正常组织中circKIF4A的表达；用siRNA敲低结直肠癌SW620细胞中circKIF4A的表达后，分别检测细胞生长、克隆形成及侵袭能力以及细胞内总谷胱甘肽（T-GSH）/氧化型谷胱甘肽（GSSG）比例与铁死亡抑制蛋白SLC7A11表达的变化；通过生物信息学软件和双荧光素酶报告基因实验预测和分析circKIF4A的目标microRNA (miRNA)以及下游的靶基因并验证。结果：与正常结直肠上皮细胞及癌旁组织比较，circKIF4A在不同直肠癌细胞系及癌组织中的表达均明显上调（均P<0.05）；敲低circKIF4A后，SW620细胞的生长、克隆形成、侵袭能力、细胞内T-GSH/GSSG比例及SLC7A11蛋白表达均明显降低（均P<0.05）；预测与分析结果显示，...

Expression and function of circular RNA KIF4A in colorectal cancer and its action mechanism

Background and Aims The circular RNA KIF4A (circKIF4A) has been found to play an important role in the malignant progression of various tumors. However, the biological role of circKIF4A in colorectal cancer has not been reported yet. Therefore, this study was conducted to investigate the effects and mechanisms of circKIF4A on the biological behavior of colorectal cancer.Methods The expressions of circKIF4A in different colorectal cancer cell lines and colonic mucosal epithelial cells as well as in colorectal cancer tissues and adjacent normal tissues were detected using qRT-PCR. After knocking down the expression of circKIF4A in colorectal cancer SW620 cells using siRNA, the cell growth, colony formation, invasion ability, as well as changes in the intracellular ratio of total glutathione (T-GSH) to oxidized glutathione (GSSG) and the expression of ferroptosis inhibitor protein SLC7A11 were detected. The target microRNAs (miRNAs) of circKIF4A and downstream target genes were predicted and analyzed using bioinformatics software and dual-luciferase reporter gene assay, and validation experiments were also perfromed.Results Compared to normal colonic epithelial cells and adjacent tissue, the expressions of circKIF4A were significantly upregulated in different colorectal cancer cell lines and cancer tissue (all P<0.05). Knockdown of circKIF4A resulted in significantly decreased cell growth, colony formation, invasion ability, intracellular T-GSH/GSSG ratio, and SLC7A11 protein expression in SW620 cells (all P<0.05). Prediction and analysis revealed the presence of a miR-515-5p binding site on the circKIF4A sequence, and SLC7A11 was identified as a downstream target gene of miR-515-5p. Validation results showed that miR-515-5p overexpression with simultaneous circKIF4A suppression had the most the inhibitory effect on SLC7A11 protein expression in SW620 cells among different treatments (P<0.05).Conclusion The expression of circKIF4A is upregulated in colorectal cancer cells and promotes the growth and invasion of colorectal cancer cells. Its mechanism may be associated with ferroptosis mediated by the circKIF4A-miR-515-5p-SLC7A11 axis.