2. Academic Validation
  3. STAT1 and m6A-mediated IL15RA upregulation promotes metastasis via ZEB1/NF-κΒ axis in ccRCC

STAT1 and m6A-mediated IL15RA upregulation promotes metastasis via ZEB1/NF-κΒ axis in ccRCC

  • Sci Rep. 2025 Oct 30;15(1):37990. doi: 10.1038/s41598-025-21947-x.
Jia Wei 1,  Xuan'er Zhao 2,  Huiping Wang 3,  Cong Wang 1,  Xinyi Liu 4,  Zimeng Shan 5,  Yican Guo 6,  Xumeng Gu 2,  Renren Li 7,  Zhansheng Zhu 8
Affiliations

Affiliations

  • 1 Laboratory of Experimental and Clinical Pathology, Department of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
  • 2 School of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, China.
  • 3 Department of Genetics, School of Life Science, Xuzhou Medical University, Xuzhou, 221004, China.
  • 4 The First School of Clinical Medicine, Xuzhou Medical University, Xuzhou, 221004, China.
  • 5 The Second School of Clinical Medicine, Xuzhou Medical University, Xuzhou, 221004, China.
  • 6 School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, China.
  • 7 Center of Healthcare Management, The Affiliated Maternity and Child Health Care Hospital of Xuzhou Medical University, Xuzhou, 221009, China. RENRENLI2023@163.com.
  • 8 Laboratory of Experimental and Clinical Pathology, Department of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China. victorzhu2013@xzhmu.edu.cn.
PMID: 41168330 DOI: 10.1038/s41598-025-21947-x
Abstract

Interleukin-15 receptor alpha (IL15RA) demonstrates critical regulatory function in oncogenesis and immunomodulation across various malignancies. However, the role of IL15RA in cancers, such as Clear Cell Renal Cell Carcinoma (ccRCC) remains unclear. Therefore, integrated pan-cancer analysis and mechanism investigation assays are essential for IL15RA-directed therapeutic strategy optimization in ccRCC. The comprehensive pan-cancer analysis reveals IL15RA as a plausible diagnostic and prognostic biomarker, as well as a promising immunotherapeutic target across various cancers, particularly ccRCC. IL15RA promotes ccRCC metastasis based on the data of the investigation. Mechanistically, STAT1 binds to IL15RA promoter region, thereby enhancing IL15RA mRNA expression, while METTL3 modulates RNA m6A methylation patterns to stabilize IL15RA transcription. Furthermore, IL15RA potentiates metastasis via NF-κΒ/ZEB1 axis in ccRCC. Drug sensitivity profiling further indicates that IL15RA expression increases sensitivity to chemotherapeutic agents in ccRCC patients. The findings demonstrate that IL15RA emerges as a critical prognostic indicator and immunotherapeutic biomarker particularly in ccRCC. Our findings underscore the necessity for comprehensive mechanistic studies to elucidate IL15RA's roles and are beneficial for advancing targeted therapeutic strategies in oncological interventions.

Keywords

Clear cell renal cell carcinoma; IL15RA; Metastasis; NF-κΒ; ZEB1; m6A.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z