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

IF 4.8 2区 医学 Q2 IMMUNOLOGY
International immunopharmacology Pub Date : 2025-01-03 Epub Date: 2024-12-09 DOI:10.1016/j.intimp.2024.113776
Wei Song, Houliang Zhang, Jinliang Ni, Huiqing Hu, Weipu Mao, Keyi Wang, Bo Peng
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引用次数: 0

Abstract

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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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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