O-GlcNAcylation of CSNK2A1 by OGT is Involved in the Progression of Colorectal Cancer.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular Biotechnology Pub Date : 2025-01-01 Epub Date: 2024-01-30 DOI:10.1007/s12033-024-01049-1
Zhengyao Yu, Huijuan He, Baoying Jiang, Jing Hu
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Abstract

Colorectal cancer (CRC) metastasis is challenging for improved clinical outcomes. The casein kinase 2 alpha 1 (CSNK2A1) is an oncogene involved in several cancers. This study aimed to investigate the influence of CSNK2A1 on CRC progression and the related molecular mechanism. The CSNK2A1 levels were predicted using bioinformatic analysis and were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell phenotypes were analyzed using cell-counting kit-8, colony formation, transwell assay, and western blot. Tumor growth was evaluated in a tumor-bearing mouse model in vivo. Similarly, O-GlcNAc modification of CSNK2A1 was assessed by immunoprecipitation, western blot, and immunofluorescence. Results indicated that CSNK2A1 was upregulated in CRC and was related to poor prognosis. Interference with CSNK2A1 suppressed CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition, inhibiting tumor growth. Moreover, OGT promoted the glycosylation modification of CSNK2A1, enhanced its protein stability, and reversed tumor progression when CSNK2A1 was knocked down. The CSNK2A1 might also affect CRC progression via the PI3K/AKT pathway. In conclusion, the OGT-O-GlcNAcylation-CSNK2A1 axis accelerated the malignant advancement of CRC, suggesting potential CRC therapeutic targets.

Abstract Image

OGT对CSNK2A1的O-GlcNAcylation参与了结直肠癌的进展。
结直肠癌(CRC)转移是改善临床疗效的一大挑战。酪蛋白激酶2α1(CSNK2A1)是一种涉及多种癌症的癌基因。本研究旨在探讨CSNK2A1对CRC进展的影响及相关分子机制。通过生物信息学分析预测了CSNK2A1的水平,并使用实时定量聚合酶链反应(qRT-PCR)进行了测定。使用细胞计数试剂盒-8、集落形成、Transwell试验和Western印迹分析细胞表型。在体内肿瘤小鼠模型中对肿瘤生长情况进行了评估。同样,通过免疫沉淀、Western 印迹和免疫荧光评估了 CSNK2A1 的 O-GlcNAc 修饰。结果表明,CSNK2A1在CRC中上调,并与不良预后有关。干扰CSNK2A1可抑制CRC细胞增殖、迁移、侵袭和上皮-间质转化,从而抑制肿瘤生长。此外,OGT还能促进CSNK2A1的糖基化修饰,增强其蛋白稳定性,并在敲除CSNK2A1后逆转肿瘤进展。CSNK2A1 还可能通过 PI3K/AKT 通路影响 CRC 的进展。总之,OGT-O-GlcNAcylation-CSNK2A1轴加速了CRC的恶性进展,提示了潜在的CRC治疗靶点。
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来源期刊
Molecular Biotechnology
Molecular Biotechnology 医学-生化与分子生物学
CiteScore
4.10
自引率
3.80%
发文量
165
审稿时长
6 months
期刊介绍: Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.
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