CYP24A1 Binding to FUS Maintains Tumor Properties by Regulating the miR-200c/ZEB1/EMT Axis

Sep 23, 2026

The active vitamin D-degrading enzyme CYP24A1 is frequently overexpressed across cancers and correlates with poor patient outcomes, yet its role in tumorigenesis and mechanism have remained insufficiently defined. High CYP24A1 mRNA levels associate with worse prognosis in ovarian cancer and lung adenocarcinoma, and CYP24A1 overexpression accelerates proliferation, migration, and invasion in vitro, while knockdown exerts anticancer effects in vitro and in vivo. CYP24A1 binds FUS via a specific amino acid motif, reducing FUS affinity for miR-200c, which releases ZEB1 from miR-200c repression to activate EMT and promote tumor progression.

LanguageEnglish

CategoryHealthcare

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Reading Time33 min

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ABSTRACT

1 | Introduction

Cancer Science ORIGINAL ARTICLE OPEN ACCESS CYP24A1 Binding to FUS Maintains Tumor Properties by Regulating the miR-200c/ZEB1/EMT Axis Ping Wang1 | Jiming Xu2,3 | Weijing You2,4 | Jie Li2 | Jing Yu2,5 | Fei Jiang1 | Zengli Zhang1 | Wentao Hu6 | Bingyan Li2 1Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China | 2Department of Nutrition and Food Hygiene, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China | 3Department of Infectious Disease Surveillance and Early Warning, Qingdao Municipal Health Commission, Qingdao, China | 4Yantai Hi-Tech Industrial Development Zone Center for Disease Control and Prevention, Yantai, China | 5Department of Clinical Laboratory Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China | 6State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China Correspondence: Wentao Hu ([wthu@suda.edu.cn](wthu@suda.edu.cn)) | Bingyan Li ([bingyanli@suda.edu.cn](bingyanli@suda.edu.cn)) Received: 31 October 2024 | Revised: 17 December 2024 | Accepted: 20 December 2024 Funding: This study was supported by National Natural Science Foundation of China (No. 12275191, U1832140, 81673151, and 81703225), in part by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) . Keywords: CYP24A1 | EMT | FUS | miR-200c | oncogene | ZEB1 ABSTRACT The active vitamin D-degrading enzyme (CYP24A1) is commonly overexpressed in various types of cancer, which is associated with poor prognosis in cancer patients. Recent studies highlight the antagonism of CYP24A1 toward the anticancer role of active vitamin D. However, the impact of CYP24A1 on tumorigenesis and its underlying mechanisms largely remains unexplored. This study also found that high CYP24A1 mRNA expressions were associated with poor prognosis in ovarian cancer and lung adenocarcinoma (LUAD) patients. Moreover, we demonstrated that the overexpression of CYP24A1 accelerated the proliferation, migration, and invasion of ovarian cancer and LUAD cancer cells in vitro. Furthermore, knockdown of CYP24A1 displayed an anticancer effector both in vitro and in vivo. Mechanically, 87–297 amino acid motif of CYP24A1 bound specifically to FUS protein, consequentially reducing FUS affinity for miR-200c. Considering FUS promotes gene silencing by binding to microRNA targets, a decrease in miR-200c levels led to a notable activation of its target ZEB1, resulting in the promotion of the epithelialmesenchymal transition (EMT) process. In conclusion, FUS binding specifically by CYP24A1 impaired miR-200c-mediated ZEB1 silencing, thereby augmenting EMT progression and tumorigenesis. These findings elucidate a fundamental mechanism by which CYP24A1 operates as an oncogene, offering potential targets for therapeutic interventions in cancer treatment. 1 | Introduction CYP24A1, cytochrome P450 family 24 subfamily A member [1], serves a critical function as an essential enzyme responsible for the degradation of the active form of vitamin D [1,25(OH)2D3], which is involved in calcium homeostasis and cellular growth processes [1–4] . Given the significant attention garnered by 1,25(OH)2D3 for its anticancer properties, the overexpression of CYP24A1 has been observed to reduce its antitumor effectiveness. Prior studies have indicated that elevated intracellular levels of CYP24A1 can lead to inadequate 1,25(OH)2D3, thereby facilitating the progression of breast cancer and papillary thyroid cancer [5, 6] . Furthermore, both upregulation of CYP24A1 and acceleration of 1,25(OH)2D3 degradation occur, consequently preserving the stem properties of glioma cells in an acidotic environment [7] . Thus, the inhibition of CYP24A1 has been | Ping Wang, Jiming Xu, and Weijing You contributed equally to this study. | | --- | | Thi

FAQs

What clinical association is reported for CYP24A1 in this study?

High CYP24A1 mRNA expression correlates with poor prognosis in ovarian cancer and lung adenocarcinoma patients.

How does CYP24A1 affect cancer cell behavior according to the abstract?

CYP24A1 overexpression accelerates proliferation, migration, and invasion in ovarian cancer and LUAD cells in vitro, while CYP24A1 knockdown shows anticancer effects both in vitro and in vivo.

What mechanistic axis connects CYP24A1 to EMT progression?

CYP24A1 binds FUS and reduces FUS affinity for miR-200c, leading to decreased miR-200c levels, activation of ZEB1, and promotion of epithelial-mesenchymal transition (EMT).

Sep 23, 2026

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