Circular RNAs (circRNAs) are involved in the regulation of many pathophysiological processes as non-coding RNAs. This study focuses on the role of circRACGAP1 in the development of non-small cell lung cancer (NSCLC). Expression patterns of circRACGAP1 and miR-144-5p in NSCLC tissues and cell lines were quantified by qRT-PCR analysis. Then, the function of circRACGAP1 on cell proliferation and tumorigenesis were confirmed in vitro and in vivo using CCK-8 assay, colony formation, EdU incorporation, and xenograft technique. The regulation of circRACGAP1 on Gefitinib resistance of NSCLC cells was evaluated by flow cytometry. The regulatory network of circRACGAP1/miR-144-5p/CDKL1 was verified by luciferase reporter assay and RNA pull-down. Western blotting analysis was performed to assess the biomarkers of cell cycle and apoptosis-associated proteins. CircRACGAP1 was highly expressed and miR-144-5p was inhibited both in NSCLC tissues and cell lines, suggesting their negative correlation in NSCLC. Knockdown of circRACGAP1 suppressed cell proliferation via arresting the cell cycle. miR-144-5p was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-144-5p directly targeted the 3′-UTR of CDKL1 to regulate cell cycle of NSCLC cells. circRACGAP1 knockdown dramatically inhibited the tumor growth and enhanced the sensitivity of NSCLC to Gefitinib in vitro and in vivo. In summary, our study revealed a novel machinery of circRACGAP1/miR-144-5p/CDKL1 for the NSCLC tumorigenesis and development, providing potential diagnostic and therapeutic targets for NSCLC.

环状 RNA (circRNA) 作为非编码 RNA 参与了许多病理生理过程的调节。本研究重点关注 circRACGAP1 在非小细胞肺癌 (NSCLC) 发展中的作用。通过qRT-PCR分析定量NSCLC组织和细胞系中circRACGAP1和miR-144-5p的表达模式。然后，使用 CCK-8 测定、集落形成、EdU 掺入和异种移植技术在体外和体内证实了 circRACGAP1 对细胞增殖和肿瘤发生的功能。通过流式细胞术评估circRACGAP1对NSCLC细胞吉非替尼耐药的调节作用。circRACGAP1/miR-144-5p/CDKL1的调控网络通过荧光素酶报告基因检测和RNA pull-down验证。进行蛋白质印迹分析以评估细胞周期和凋亡相关蛋白的生物标志物。CircRACGAP1 在 NSCLC 组织和细胞系中高表达，miR-144-5p 被抑制，表明它们在 NSCLC 中呈负相关。circRACGAP1 的敲除通过阻止细胞周期来抑制细胞增殖。miR-144-5p 被确定为逆转 circRACGAP1 介导的细胞增殖的下游靶标。miR-144-5p直接靶向CDKL1的3'-UTR以调节NSCLC细胞的细胞周期。circRACGAP1 敲低显着抑制了肿瘤生长并增强了 NSCLC 在体外和体内对吉非替尼的敏感性。总之，我们的研究揭示了 circRACGAP1/miR-144-5p/CDKL1 用于 NSCLC 肿瘤发生和发展的新机制，为 NSCLC 提供了潜在的诊断和治疗靶点。提示它们在非小细胞肺癌中呈负相关。circRACGAP1 的敲除通过阻止细胞周期来抑制细胞增殖。miR-144-5p 被确定为逆转 circRACGAP1 介导的细胞增殖的下游靶标。miR-144-5p直接靶向CDKL1的3'-UTR以调节NSCLC细胞的细胞周期。circRACGAP1 敲低显着抑制了肿瘤生长并增强了 NSCLC 在体外和体内对吉非替尼的敏感性。总之，我们的研究揭示了 circRACGAP1/miR-144-5p/CDKL1 用于 NSCLC 肿瘤发生和发展的新机制，为 NSCLC 提供了潜在的诊断和治疗靶点。提示它们在非小细胞肺癌中呈负相关。circRACGAP1 的敲除通过阻止细胞周期来抑制细胞增殖。miR-144-5p 被确定为逆转 circRACGAP1 介导的细胞增殖的下游靶标。miR-144-5p直接靶向CDKL1的3'-UTR以调节NSCLC细胞的细胞周期。circRACGAP1 敲低显着抑制了肿瘤生长并增强了 NSCLC 在体外和体内对吉非替尼的敏感性。总之，我们的研究揭示了 circRACGAP1/miR-144-5p/CDKL1 用于 NSCLC 肿瘤发生和发展的新机制，为 NSCLC 提供了潜在的诊断和治疗靶点。miR-144-5p 被确定为逆转 circRACGAP1 介导的细胞增殖的下游靶标。miR-144-5p直接靶向CDKL1的3'-UTR以调节NSCLC细胞的细胞周期。circRACGAP1 敲低显着抑制了肿瘤生长并增强了 NSCLC 在体外和体内对吉非替尼的敏感性。总之，我们的研究揭示了 circRACGAP1/miR-144-5p/CDKL1 用于 NSCLC 肿瘤发生和发展的新机制，为 NSCLC 提供了潜在的诊断和治疗靶点。miR-144-5p 被确定为逆转 circRACGAP1 介导的细胞增殖的下游靶标。miR-144-5p直接靶向CDKL1的3'-UTR以调节NSCLC细胞的细胞周期。circRACGAP1 敲低显着抑制了肿瘤生长并增强了 NSCLC 在体外和体内对吉非替尼的敏感性。总之，我们的研究揭示了 circRACGAP1/miR-144-5p/CDKL1 用于 NSCLC 肿瘤发生和发展的新机制，为 NSCLC 提供了潜在的诊断和治疗靶点。