O-GlcNAcylation of hexokinase 2 modulates mitochondrial dynamics and enhances the progression of lung cancer.

IF 3.5 2区 生物学 Q3 CELL BIOLOGY Molecular and Cellular Biochemistry Pub Date : 2024-11-04 DOI:10.1007/s11010-024-05146-2
S I Panpan, G E Wei, W U Kaiming, Renquan Zhang
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Abstract

Non-small cell lung cancer (NSCLC) stands as the prevailing manifestation of lung cancer, with current therapeutic modalities linked to a dismal prognosis, necessitating further advancements. Hexokinase 2 (HK2), a critical enzyme positioned on the mitochondrial membrane, exerts control over diverse biological pathways, thereby regulating cancer. Nevertheless, the precise role and mechanism of HK2 in NSCLC remain inadequately elucidated, warranting comprehensive investigation. HK2 expression in NSCLC tissues and cell lines was detected through immunohistochemistry and western blot analysis. Concurrently, shRNA assays were applied to scrutinize the impact of HK2 on cell proliferation, apoptosis, migration, and invasion processes in NSCLC cell lines, utilizing CCK8, flow cytometry, wound-healing assay, and transwell techniques. The involvement of HK2 in mitochondrial dynamics was probed through western blot analysis, mitochondrial membrane potential assay, and assessment of ROS generation. Next, the functional role of HK2 was assessed by examining its influence on xenograft tumor growth in nude mice in vivo. Further research has demonstrated that HK2 played a role in NSCLC through its O-GlcNAcylation process. The results of the study revealed that HK2 O-GlcNAcylation promoted the proliferation, migration, and invasive characteristics of NSCLC cells, while alleviating mitochondrial damage, whereas O-GlcNAcylation inactivation yielded the opposite effect. Furthermore, in vivo experiments in nude mice illustrated that HK2 O-GlcNAcylation could stimulate tumor growth in NSCLC. These results suggested that HK2 may impact mitochondrial dynamics in NSCLC through its O-GlcNAcylation, thereby contributing to the progression of NSCLC.

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己糖激酶 2 的 O-GlcNAcylation 可调节线粒体动力学并促进肺癌的进展。
非小细胞肺癌(NSCLC)是肺癌的主要表现形式,目前的治疗方法预后不佳,需要进一步研究。六磷酸酶 2(HK2)是一种位于线粒体膜上的关键酶,可控制多种生物通路,从而调节癌症。然而,HK2 在 NSCLC 中的确切作用和机制仍未得到充分阐明,值得进行全面研究。通过免疫组化和免疫印迹分析检测了 HK2 在 NSCLC 组织和细胞系中的表达。同时,利用CCK8、流式细胞术、伤口愈合试验和透孔技术,应用shRNA检测HK2对NSCLC细胞系的细胞增殖、凋亡、迁移和侵袭过程的影响。通过 Western 印迹分析、线粒体膜电位检测和 ROS 生成评估,研究了 HK2 参与线粒体动力学的情况。接着,通过检测 HK2 对体内裸鼠异种移植肿瘤生长的影响,评估了 HK2 的功能作用。进一步的研究表明,HK2 通过其 O-GlcNAcylation 过程在 NSCLC 中发挥作用。研究结果显示,HK2 O-GlcNAcylation能促进NSCLC细胞的增殖、迁移和侵袭特性,同时减轻线粒体损伤,而O-GlcNAcylation失活则产生相反的效果。此外,裸鼠体内实验表明,HK2 O-GlcNAcylation可刺激NSCLC的肿瘤生长。这些结果表明,HK2 可能通过其 O-GlcNAcylation 影响 NSCLC 的线粒体动力学,从而导致 NSCLC 的恶化。
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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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Retraction Note: MiR-146a negatively regulates neutrophil elastase-induced MUC5AC secretion from 16HBE human bronchial epithelial cells. Retraction Note: Topical application of aminopeptidase N-neutralizing antibody accelerates wound closure. Correction to: Mitochondrial complex-1 as a therapeutic target for cardiac diseases. RETRACTED ARTICLE: Upregulation of MCL-1 by LUCAT1 through interacting with SRSF1 promotes the migration and invasion in non-small cell lung carcinoma. Functional activity and morphology of isolated rat cardiac mitochondria under calcium overload. Effect of naringin.
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