Song Wei, Zhang Houliang, Ni Jinliang, Hu Huiqing, Mao Weipu, Wang Keyi, Peng Bo
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.
Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing 210009, China.
Int Immunopharmacol. 2025 Jan 3;145:113776. doi: 10.1016/j.intimp.2024.113776. Epub 2024 Dec 9.
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.
众所周知，ALKBH5在各类肿瘤的恶性进展中起着关键作用。然而，其在透明细胞肾细胞癌（ccRCC）中的作用及潜在调控机制仍不清楚。在本研究中，我们运用了一系列技术，包括蛋白质印迹法、实时定量PCR、银染、质谱分析、免疫共沉淀（Co-IP）、GST下拉实验和免疫荧光，来研究ALKBH5在ccRCC中的功能，并阐明其中涉及的具体机制。我们的结果表明，ALKBH5在ccRCC中的表达显著上调。体外实验显示，ALKBH5促进肿瘤增殖、侵袭、迁移和干性。在体内，ALKBH5被证明可促进肿瘤生长和肺转移。从机制上讲，我们的研究表明，ALKBH5通过与不均一核核糖核蛋白D样蛋白（HNRNPDL）结合，促进MEK、ERK和p38的核转位，并激活下游靶点如c-Myc和PCNA，从而加速ccRCC的恶性进展。
