RANBP2 Activates O-GlcNAcylation through Inducing CEBPα-Dependent OGA Downregulation to Promote Hepatocellular Carcinoma Malignant Phenotypes

Liu, Xiaoming; Chen, Xingyu; Xiao, Mengqing; Zhu, Yuxing; Gong, Rui; Liu, Jianye; Zeng, Qinghai; Xu, Canxia; Chen, Xiong; Wang, Fen Wei; Cao, Ke

doi:10.3390/cancers13143475

Cited by 13 publications

(6 citation statements)

References 39 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the gene is implicated in some tumorigenic pathways, for example, indirectly in the p53 and PI3K/Akt pathways ( 46 , 47 ). Recently, there has been increasing evidence to show that the upregulation of RANBP2 promotes cancer cell growth in cholangiocarcinoma, cervical cancer, and hepatocellular carcinoma ( 48 - 50 ). From the present study, it is evident that RANBP2 serving as an upregulated gene may impact tamoxifen resistance.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes involved in tamoxifen-resistant breast cancer using bioinformatics analysis

Wang¹,

Wang²

2021

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background The purpose of the present study was to investigate the molecular mechanisms of tamoxifen resistance in breast cancer and to identify potential targets for antitamoxifen resistance. Methods Differentially expressed genes (DEGs) in tamoxifen-resistant and tamoxifen-sensitive breast cancer cells were assessed using the GSE67916 dataset acquired from the Gene Expression Omnibus database. Gene ontology (GO) and pathway enrichment analyses were applied to investigate the functions and pathways of the DEGs. Subsequently, the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING), and subnetworks were further analyzed by Molecular Complex Detection (MCODE). The PPI network and subnetworks were visualized using Cytoscape software. Results In total, 438 DEGs were identified, of which 300 were upregulated and 138 were downregulated. The DEGs were significantly enriched in the protein binding, cellular response to estradiol stimulus, and immune response GO terms while the most significant pathways included the mitogen-activated protein kinase (MAPK) signaling pathway in cancer. The PPI network of DEGs was constructed with 288 nodes and 629 edges, and 2 subnetworks were screened out from the entire network. Conclusions A number of significant hub DEGs were identified based on their degree of connectivity in the PPI network, , included MAPK1 (node degree 36), ESR1 (node degree 27), SMARCA4 (node degree 27), RANBP2 (node degree 25), and PRKCA (node degree 21). These critical hub genes were found to be related to tamoxifen resistance in breast cancer. The results of this study further the understanding of tamoxifen resistance at the molecular level and identify potential therapeutic targets for tamoxifen-resistant breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of key genes involved in tamoxifen-resistant breast cancer using bioinformatics analysis

Wang¹,

Wang²

2021

Transl Cancer Res TCR

View full text Add to dashboard Cite

show abstract

“…Contradicting roles have been reported for RANBP2 in cancer, as both a tumor suppressor and an oncogenic role have been described. RANBP2 has been reported to be upregulated in cervical cancer cells [102], and to promote cancer progression by regulating gene expression [103,104] and nucleocytoplasmic translocation [101]. In contrast, RANBP2 has a tumor‐suppressor role by SUMOylating proteins such as Topoisomerase IIα [56], PML‐IV [105], and the transcriptional repressor small heterodimer partner [100].…”

Section: Human Diseases Linked To Ranbp2mentioning

confidence: 99%

RANBP2 evolution and human disease

Desgraupes,

Etienne,

Arhel

2023

FEBS Letters

View full text Add to dashboard Cite

RANBP2/Nup358 (Ran Binding Protein 2) is a nucleoporin and a key component of the nuclear pore complex. Through its multiple functions (e.g. SUMOylation, regulation of nucleocytoplasmic transport) and subcellular localizations (e.g. at the nuclear envelope, kinetochores, annulate lamellae), it is involved in many cellular processes. RANBP2 dysregulation or mutation leads to the development of human pathologies, such as Acute Necrotizing Encephalopathy 1 (ANE1), cancer, neurodegenerative diseases and it is also involved in viral infections. The chromosomal region containing the RANBP2 gene is highly dynamic, with high structural variation and recombination events that led to the appearance of a gene family called RGPD (RANBP2 and GCC2 Protein Domains), with multiple gene loss/duplication events during ape evolution. Although RGPD homoplasy and maintenance during evolution suggest they might confer an advantage to their hosts, their functions are still unknown and understudied. In this review, we discuss the appearance and importance of RANBP2 in metazoans and its function‐related pathologies, caused by an alteration of its expression levels (through promotor activity, post‐transcriptional or post‐translational modifications), its localization or genetic mutations.

show abstract

“…Several studies have reported that hyper O ‐GlcNAcylation seems to be a common feature in a variety of cancers, including liver cancer, 35,177 breast cancer, 13 uterine cancer, 178 prostatic cancer, 179 colorectal cancer 180 and pancreatic cancer, 94,181 and even non‐solid cancers such as acute myeloid leukaemia and other blood cancers 26,182 . Hyper O‐ GlcNAcylation in cancer cells is mainly attributed to disruption of O ‐GlcNAcylation cycle homeostasis and abnormal expression of its process enzymes 183 .…”

Section: Hyper O‐glcnacylation Is a Pivotal Potential Pathological Fa...mentioning

confidence: 99%

Protein O‐GlcNAcylation: The sweet hub in liver metabolic flexibility from a (patho)physiological perspective

Hu,

Zhang,

et al. 2023

Liver International

View full text Add to dashboard Cite

O‐GlcNAcylation is a dynamic, reversible and atypical O‐glycosylation that regulates various cellular physiological processes via conformation, stabilisation, localisation, chaperone interaction or activity of target proteins. The O‐GlcNAcylation cycle is precisely controlled by collaboration between O‐GlcNAc transferase and O‐GlcNAcase. Uridine‐diphosphate‐N‐acetylglucosamine, the sole donor of O‐GlcNAcylation produced by the hexosamine biosynthesis pathway, is controlled by the input of glucose, glutamine, acetyl coenzyme A and uridine triphosphate, making it a sensor of the fluctuation of molecules, making O‐GlcNAcylation a pivotal nutrient sensor for the metabolism of carbohydrates, amino acids, lipids and nucleotides. O‐GlcNAcylation, particularly prevalent in liver, is the core hub for controlling systemic glucose homeostasis due to its nutritional sensitivity and precise spatiotemporal regulation of insulin signal transduction. The pathology of various liver diseases has highlighted hepatic metabolic disorder and dysfunction, and abnormal O‐GlcNAcylation also plays a specific pathological role in these processes. Therefore, this review describes the unique features of O‐GlcNAcylation and its dynamic homeostasis maintenance. Additionally, it explains the underlying nutritional sensitivity of O‐GlcNAcylation and discusses its mechanism of spatiotemporal modulation of insulin signal transduction and liver metabolic homeostasis during the fasting and feeding cycle. This review emphasises the pathophysiological implications of O‐GlcNAcylation in nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and hepatic fibrosis, and focuses on the adverse effects of hyper O‐GlcNAcylation on liver cancer progression and metabolic reprogramming.

show abstract

RANBP2 Activates O-GlcNAcylation through Inducing CEBPα-Dependent OGA Downregulation to Promote Hepatocellular Carcinoma Malignant Phenotypes

Cited by 13 publications

References 39 publications

Identification of key genes involved in tamoxifen-resistant breast cancer using bioinformatics analysis

Identification of key genes involved in tamoxifen-resistant breast cancer using bioinformatics analysis

RANBP2 evolution and human disease

Protein O‐GlcNAcylation: The sweet hub in liver metabolic flexibility from a (patho)physiological perspective

Contact Info

Product

Resources

About