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

被引:0
作者
Song, Wei [1 ,2 ]
Zhang, Houliang [3 ]
Ni, Jinliang [1 ,2 ]
Hu, Huiqing [5 ]
Mao, Weipu [3 ]
Wang, Keyi [4 ]
Peng, Bo [1 ,2 ]
机构
[1] Tongji Univ, Shanghai Putuo Dist Peoples Hosp, Sch Med, Dept Urol, 1291 Jiangning Rd, Shanghai 200060, Peoples R China
[2] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Urol, 301 Yanchang Middle Rd, Shanghai 200072, Peoples R China
[3] Southeast Univ, Affiliated Zhongda Hosp, Dept Urol, 87 Dingjiaqiao,Hunan Rd, Nanjing 210009, Peoples R China
[4] Fudan Univ, Zhongshan Hosp, Sch Med, Dept Urol, Shanghai 200032, Peoples R China
[5] Shanghai Jiao Tong Univ, Peoples Hosp 6, Sch Med, Dept Ultrasound, Shanghai 200240, Peoples R China
关键词
AlkB homologue H5; Clear cell renal cell carcinoma; Heterogeneous nuclear ribonucleoprotein D-like; Mitogen-activatedproteinkinase; Progression; MYC; OVEREXPRESSION; METASTASIS; EXPRESSION;
D O I
10.1016/j.intimp.2024.113776
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页数:12
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