<scp>HROB</scp> Induces Lung Adenocarcinoma Progression via <scp>ZC3HC1</scp>‐<scp>CCNB1</scp> Axis Regulation and Cell Cycle Dysregulation
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.
Authors
- Xinhang Hu
- Yuanwei Guo
- Shouzhi Xie
- Bing Xiao (ORCID: https://orcid.org/0000-0001-6572-5641)
- Yupeng Jiang (ORCID: https://orcid.org/0000-0001-8971-2079)
- Xingchun Huang
- Fenglei Yu (ORCID: https://orcid.org/0000-0003-3409-065X)
- Bin Wang (ORCID: https://orcid.org/0000-0001-8863-9738)
- Li Wang (ORCID: https://orcid.org/0000-0002-8625-9659)
- Chéng Wáng (ORCID: https://orcid.org/0000-0002-0178-8317)
- Zhi Hong Yang
- Zhe Zhang (ORCID: https://orcid.org/0009-0004-9608-6626)
Institutions
- Central South University (CN)
- Guilin Medical University (CN)
- Hunan Cancer Hospital (CN)
- Second Xiangya Hospital of Central South University (CN)
Publication Details
- Journal
- Cancer Science
- Published
- 2025-07-14
- DOI
- https://doi.org/10.1111/cas.70141
- Primary Topic
- Ubiquitin and proteasome pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Hunan Province
- Key Research and Development Program of Hunan Province of China