HROB Induces Lung Adenocarcinoma Progression via ZC3HC1-CCNB1 Axis Regulation and Cell Cycle Dysregulation

IF 4.3 2区医学 Q1 ONCOLOGY

Cancer Science Pub Date : 2025-07-14 DOI:10.1111/cas.70141

Zhe Zhang, Cheng Wang, Yuanwei Guo, Zhenyu Zhao, Zhi Yang, Shouzhi Xie, Xinhang Hu, Xingchun Huang, Yupeng Jiang, Bing Xiao, Li Wang, Fenglei Yu, Bin Wang

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引用次数: 0

Abstract

Lung adenocarcinoma (LUAD), a leading cause of cancer-related mortality, remains a significant global health challenge due to limited understanding of its molecular mechanisms. HROB, a recently identified gene, has been implicated in cell cycle regulation, but its role in lung cancer progression is poorly understood. In this study, we demonstrate that HROB suppresses LUAD progression by interacting with ZC3HC1 and reducing its phosphorylation at Ser354. This de-phosphorylation event facilitates K27-linked ubiquitination of CCNB1, promoting its proteasomal degradation and impairing the G2-to-M phase transition. Consequently, HROB suppresses cell proliferation and tumor growth. Our findings reveal a novel HROB–ZC3HC1–CCNB1 regulatory axis, providing mechanistic insights into LUAD progression. These results highlight HROB as a potential therapeutic target, offering new avenues for clinical intervention in lung cancer treatment.

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HROB通过ZC3HC1-CCNB1轴调控和细胞周期失调诱导肺腺癌进展。

肺腺癌（LUAD）是癌症相关死亡的主要原因，由于对其分子机制的了解有限，仍然是一个重大的全球健康挑战。HROB是最近发现的一种基因，与细胞周期调节有关，但其在肺癌进展中的作用尚不清楚。在这项研究中，我们证明了HROB通过与ZC3HC1相互作用并降低其Ser354位点的磷酸化来抑制LUAD的进展。这种去磷酸化事件促进了k27相关的CCNB1泛素化，促进了其蛋白酶体降解并损害了g2到m的相变。因此，HROB抑制细胞增殖和肿瘤生长。我们的研究结果揭示了一个新的h罗伯- zc3hc1 - ccnb1调节轴，为LUAD的进展提供了机制见解。这些结果突出了HROB作为潜在的治疗靶点，为临床干预肺癌治疗提供了新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Science 医学-肿瘤学

自引率

3.50%

发文量

406

审稿时长

2 months

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.