Rationale: Radioresistance remains the major cause of local relapse and distant metastasis in lung cancer. However, the underlying molecular mechanisms remain poorly defined. This study aimed to investigate the role and regulatory mechanism of Cyclin K in lung cancer radioresistance./nMethods: Expression levels of Cyclin K were measured by immunohistochemistry in human lung cancer tissues and adjacent normal lung tissues. Cell growth and proliferation, neutral comet and foci formation assays, G2/M checkpoint and a xenograft mouse model were used for functional analyses. Gene expression was examined by RNA sequencing and quantitative real-time PCR. Protein-protein interaction was assessed by immunoprecipitation and GST pull-down assays./nResults: We report that Cyclin K is frequently overexpressed and correlates with poor prognosis in lung cancer patients. Functionally, we demonstrate that Cyclin K depletion results in reduced proliferation, defective G2/M checkpoint and enhanced radiosensitivity in lung cancer. Mechanistically, we reveal that Cyclin K interacts with and promotes the stabilization of β-catenin protein, thereby upregulating the expression of Cyclin D1. More importantly, we show that Cyclin D1 is the major effector that mediates the biological functions of Cyclin K in lung cancer./nConclusions: These findings suggest that Cyclin K positively modulates the β-catenin/Cyclin D1 axis to promote tumorigenesis and radioresistance in lung cancer, indicating that Cyclin K may represent a novel attractive biomarker for lung cancer radiotherapy.

中文翻译：

---

Cyclin K与β-catenin相互作用以诱导Cyclin D1表达并促进肺癌的肿瘤发生和放射抵抗

理由：放射抵抗仍然是肺癌局部复发和远处转移的主要原因。但是，潜在的分子机制仍然不清楚。本研究旨在探讨Cyclin K在肺癌放射线耐药中的作用及其调控机制。方法：采用免疫组织化学方法检测Cyclin K在人肺癌组织和正常肺组织中的表达水平。使用细胞生长和增殖，中性彗星和病灶形成分析，G2 / M检查点和异种移植小鼠模型进行功能分析。通过RNA测序和定量实时PCR检查基因表达。蛋白质相互作用进行了评估通过免疫沉淀和GST下拉assays./n结果：我们报告说，Cyclin K经常过度表达，并与肺癌患者的不良预后相关。在功能上，我们证明细胞周期蛋白K耗竭导致增殖减少，G2 / M检查点缺陷和肺癌的放射敏感性增强。从机理上讲，我们发现Cyclin K与β-catenin蛋白相互作用并促进其稳定，从而上调了Cyclin D1的表达。更重要的是，我们证明Cyclin D1是介导肺癌中Cyclin K生物学功能的主要效应子。/n结论：这些发现表明，Cyclin K积极调节β-catenin/ Cyclin D1轴，从而促进肺癌的发生和放射抵抗。肺癌，这表明细胞周期蛋白K可能代表肺癌放疗的一种新颖的有吸引力的生物标记。