ALKBH5 promotes malignant proliferation of renal clear cell carcinoma by activating the MAPK pathway through binding to HNRNPDL.

Autor: Song W; Department of Urology, Shanghai Putuo District People's Hospital, School of Medicine, Tongji University, 1291 Jiangning Road, Pu'tuo District, Shanghai 200060, China; Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301, Yanchang Middle Road, 200072 Shanghai, China., Zhang H; Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing 210009, China., Ni J; Department of Urology, Shanghai Putuo District People's Hospital, School of Medicine, Tongji University, 1291 Jiangning Road, Pu'tuo District, Shanghai 200060, China; Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301, Yanchang Middle Road, 200072 Shanghai, China., Hu H; Department of Ultrasound, The Sixth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240, China., Mao W; Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing 210009, China. Electronic address: maoweipu88@163.com., Wang K; Department of Urology, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai 200032, China. Electronic address: wangkeyi_tongji@tonyji.edu.cn., Peng B; Department of Urology, Shanghai Putuo District People's Hospital, School of Medicine, Tongji University, 1291 Jiangning Road, Pu'tuo District, Shanghai 200060, China; Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301, Yanchang Middle Road, 200072 Shanghai, China. Electronic address: pengbo6908@tongji.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2025 Jan 03; Vol. 145, pp. 113776. Date of Electronic Publication: 2024 Dec 09.
DOI: 10.1016/j.intimp.2024.113776
Abstrakt: It is well established that ALKBH5 plays a crucial role in the malignant progression of various types of tumors. However, its role in clear cell renal cell carcinoma (ccRCC) and the underlying regulatory mechanisms remain unclear. In this study, we employed a range of techniques, including protein blotting, real-time quantitative PCR, silver staining, mass spectrometry, co-immunoprecipitation (Co-IP), GST-pull down, and immunofluorescence, to investigate the functions of ALKBH5 in ccRCC and elucidate the specific mechanisms involved. Our results demonstrated that ALKBH5 expression was significantly upregulated in ccRCC. In vitro experiments revealed that ALKBH5 promoted tumor proliferation, invasion, migration, and stemness. In vivo, ALKBH5 was shown to enhance tumor growth and lung metastasis. Mechanistically, our studies suggest that ALKBH5 accelerates the malignant progression of ccRCC by binding to heterogeneous nuclear ribonucleoprotein D-like (HNRNPDL), facilitating the nuclear translocation of MEK, ERK, and p38, and activating downstream targets such as c-Myc and PCNA.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: