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HK2 expression was assessed in NSCLC tissues and cell lines, while shRNA was used to examine effects on proliferation, apoptosis, migration, invasion, mitochondrial function, ROS, and xenograft tumor growth. Results indicate that HK2 O-GlcNAcylation promotes malignant phenotypes and stimulates tumor growth while reducing mitochondrial damage, whereas inactivation produces opposite effects, implicating HK2 O-GlcNAcylation in mitochondrial dynamics-driven NSCLC progression.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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role does HK2 O-GlcNAcylation play in NSCLC cell behavior?","Question",{"text":63,"@type":64},"HK2 O-GlcNAcylation increases NSCLC cell proliferation, migration, and invasive properties, while O-GlcNAcylation inactivation produces the opposite effects.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was the impact of HK2 on mitochondrial dynamics investigated?",{"text":68,"@type":64},"Mitochondrial dynamics and related function were examined using western blot analysis, mitochondrial membrane potential assays, and measurements of ROS generation.",{"name":70,"@type":61,"acceptedAnswer":71},"What evidence links HK2 O-GlcNAcylation to tumor progression in vivo?",{"text":72,"@type":64},"In nude mice xenograft experiments, HK2 O-GlcNAcylation enhanced tumor growth in NSCLC, supporting its role in disease progression.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},333009,1790857084,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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of lung cancer  \nS. I. Panpan1 · G. E. Wei1 · W. U. Kaiming1 · Renquan Zhang1  \nReceived: 2 July 2024 / Accepted: 21 October 2024 / Published online: 4 November 2024 © The Author(s) 2024  \nAbstract  \nNon-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-GlcNAcylationinactivation 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.  \nKeywords Hexokinase 2 · O-GlcNAcylation · Mitochondrial dynamics · NSCLC  \nIntroduction  \nGlobally, lung cancer presents a major public health issue, standing as the primary reason for cancer-related fatalities [1, 2]. Its high incidence and mortality rates pose a grave risk to human well-being. Non-small cell lung cancer (NSCLC) is considered the predominant form of lung cancer, accounting for around 80% of all cases [3] . Despite some progress made in the past few decades, such as smoking control [4] and early screening [5–7], the treatment of NSCLC remains challenging. Therefore, it is crucial to strengthen research and practice in NSCLC prevention, early diagnosis, and treatment to decrease the frequency and mortality  \n* Renquan Zhang [zhangrenquanayfy@163.com](zhangrenquanayfy@163.com)  \n1 Department of Chest Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui, China  \nrates of lung cancer and improve the overall health status of individuals.  \nO-GlcNAcylation is an emerging post-translational modification of protein serine and threonine residues [8] . The dynamic interplay between O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (OGA) regulates the addition and removal of O-GlcNAc moieties on protein substrates [9 , 10] . Recent research suggests alterations in O-GlcNAcylation levels within cancer cells, underscoring the potential significance of this modification in oncogenesis [11, 12] . Primarily, O-GlcNAcylation exerted an influence on cancer cell proliferation, metastasis, and apoptosis [13–15] . Investigations have revealed that O-GlcNAcylation can regulate the glycolytic pathway and lipid metabolic pathway of cancer cells, thus influencing the energy metabolism and growth of cancer cells [10, 16, 17] . In addition, O-GlcNAcylation can also affect the oxidative phosphorylation process and immune escape and other processes in cancer cells, thus affecting the metabolic path","cbCaipm3ib7bBPch","https://ap.wps.com/l/cbCaipm3ib7bBPch","pdf",8167308,11,"English","# Abstract\n# Introduction\n# Materials and methods\n## Clinical samples\n## Cell culture and treatment","[{\"question\":\"What role does HK2 O-GlcNAcylation play in NSCLC cell behavior?\",\"answer\":\"HK2 O-GlcNAcylation increases NSCLC cell proliferation, migration, and invasive properties, while O-GlcNAcylation inactivation produces the opposite effects.\"},{\"question\":\"How was the impact of HK2 on mitochondrial dynamics investigated?\",\"answer\":\"Mitochondrial dynamics and related function were examined using western blot analysis, mitochondrial membrane potential assays, and measurements of ROS generation.\"},{\"question\":\"What evidence links HK2 O-GlcNAcylation to tumor progression in vivo?\",\"answer\":\"In nude mice xenograft experiments, HK2 O-GlcNAcylation enhanced tumor growth in NSCLC, supporting its role in disease progression.\"}]","O-GlcNAcylation of Hexokinase 2 Modulates Mitochondrial Dynamics and Enhances the Progression of Lung Cancer | PDF",1790000338,28]