环状RNA circLIMK1-005通过与RPA1蛋白相互作用激活CDK4信号传导,促进肺腺癌的进展。

IF 7 2区 生物学 Q1 CELL BIOLOGY
Xia Yang, Lu Liu, Zhongjian Yu, Yuanlin Chen, Shiting Xu, Meiyuan Liu, Meng Wang, Huili Guo, Zhiwu Zhang, Bingjie Shan, Silin Cai, Mengting Pan, Jiangyu Zhang, Fengpin Wang, Yanfang Zheng
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引用次数: 0

摘要

肺腺癌(LUAD)是全球癌症死亡的主要原因。环状rna (circRNAs)在各种癌症的发生和发展中已经成为潜在的关键角色。然而,circrna在LUAD中的具体作用和机制在很大程度上仍未被探索。在这里,我们旨在阐明一种特殊的新型circRNA circLIMK1-005 (hsa_circ_0002690)在LUAD发病机制中的作用。我们的研究显示circLIMK1-005在LUAD中表达上调,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。从机制上讲,circLIMK1-005提高了Cyclin D1和CDK4蛋白的表达,从而激活了CDK4信号传导。我们进一步证明circLIMK1-005通过与RPA1蛋白结合并激活CDK4途径来促进LUAD的进展。体内实验证实了这些发现,证实circLIMK1-005/RPA1/CDK4轴促进了LUAD的进展,并与不良的临床结果相关。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患者的潜在治疗策略。LUAD进展中circLIMK1-005/RPA1/CDK4轴相关假说示意图。图是用BioGDP.com创建的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circular RNA circLIMK1-005 promotes the progression of lung adenocarcinoma by interacting with RPA1 protein to activate CDK4 signaling.

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.

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来源期刊
Cell Death Discovery
Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
8.30
自引率
1.40%
发文量
468
审稿时长
9 weeks
期刊介绍: Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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