Yang Xia, Liu Lu, Yu Zhongjian, Chen Yuanlin, Xu Shiting, Liu Meiyuan, Wang Meng, Guo Huili, Zhang Zhiwu, Shan Bingjie, Cai Silin, Pan Mengting, Zhang Jiangyu, Wang Fengpin, Zheng Yanfang
Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China.
Cell Death Discov. 2025 Jul 1;11(1):297. doi: 10.1038/s41420-025-02565-y.
Lung adenocarcinoma (LUAD) is the leading cause of cancer death worldwide. Circular RNAs (circRNAs) have emerged as potential key players in the onset and progression of various cancers. However, the specific roles and mechanisms of circRNAs in LUAD remain largely unexplored. Here, we aimed to elucidate the role of a particular novel circRNA, circLIMK1-005 (hsa_circ_0002690), in the pathogenesis of LUAD. Our study revealed that circLIMK1-005 was upregulated in LUAD and correlated with poor patient prognosis. Functionally, circLIMK1-005 significantly promoted LUAD cell proliferation and metastasis. Mechanistically, circLIMK1-005 elevated the expression of Cyclin D1 and CDK4 proteins, thereby activating CDK4 signaling. We further demonstrated that circLIMK1-005 promoted LUAD progression by binding with RPA1 protein and activating the CDK4 pathway. In vivo experiments corroborated these findings, confirming that the circLIMK1-005/RPA1/CDK4 axis contributed to LUAD progression and was associated with poor clinical outcomes. Our study revealed a novel mechanism of the circLIMK1-005/RPA1/CDK4 axis in LUAD progression, and highlighted that targeting circLIMK1-005 could represent a potential therapeutic strategy for patients with LUAD. Schematic diagram of hypothesis involved in the circLIMK1-005/RPA1/CDK4 axis in LUAD progression. Figure was created with BioGDP.com.
肺腺癌（LUAD）是全球癌症死亡的主要原因。环状RNA（circRNAs）已成为各种癌症发生和发展中的潜在关键因素。然而，circRNAs在LUAD中的具体作用和机制仍 largely未被探索。在此，我们旨在阐明一种特定的新型circRNA，即circLIMK1 - 005（hsa_circ_0002690）在LUAD发病机制中的作用。我们的研究表明，circLIMK1 - 005在LUAD中上调，并与患者预后不良相关。在功能上，circLIMK1 - 005显著促进LUAD细胞增殖和转移。机制上，circLIMK1 - 005提高了细胞周期蛋白D1和CDK4蛋白的表达，从而激活CDK4信号通路。我们进一步证明，circLIMK1 - 005通过与RPA1蛋白结合并激活CDK4途径促进LUAD进展。体内实验证实了这些发现，确认circLIMK1 - 005/RPA1/CDK4轴促成了LUAD进展，并与不良临床结果相关。我们的研究揭示了circLIMK1 - 005/RPA1/CDK4轴在LUAD进展中的新机制，并强调靶向circLIMK1 - 005可能代表LUAD患者的一种潜在治疗策略。LUAD进展中circLIMK1 - 005/RPA1/CDK4轴所涉及假设的示意图。图由BioGDP.com创建。
