Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF‐beta and AKT/mTOR signaling pathways

Li, Shijie; Pan, Zhifang; Qin, Kang; Guo, Hua; Yang, Qingcheng; Cheng, Dongdong

doi:10.1002/ctm2.377

Cited by 9 publications

(5 citation statements)

References 49 publications

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“…This abnormal fusion gene is also thought to be a major factor in congenital primitive plasmacytoid dendritic cell tumors ( 59 ). The high expression of CLTC has also been shown to be an independent prognostic factor for tumor-free survival and overall survival in patients with osteosarcoma ( 60 ). Transcriptome analysis revealed that CLTC–TFE3 fusion is present in renal cancer and affects many downstream cancer-related pathways ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes Associated With the Development of Stomach Adenocarcinoma by Integrated Bioinformatics Analysis

et al. 2022

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ObjectiveThis study was conducted in order to gain a better understanding of the molecular mechanisms of stomach adenocarcinoma (STAD), which is necessary to predict the prognosis of STAD and develop novel gene therapy strategies.MethodsIn this study, the gene expression profile of GSE118916 in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas Program (TCGA) was used to explore the differential co-expression genes of STAD and normal tissues.ResultsA total of 407 STAD samples were collected, consisting of 375 from stomach adenocarcinoma tissues and 32 from normal tissues, as well as RNA-seq count data for 19,600 genes. Forty-two differentially expressed genes were screened by weighted gene co-expression network analysis (WGCNA) and differentially expressed gene analysis. According to the functional annotation analysis of the clusterProfiler R package, these genes were analyzed for GO function enrichment, digestion (biological process), tube bottom material membrane (cell component), and oxidoreductase activity (molecular function). The KEGG pathway was enriched in gastric acid secretion and chemical carcinogenesis. In addition, Cytoscape’s cytoHubba plug-in was used to identify seven hub genes (EWSR1, ESR1, CLTC, PCMT1, TP53, HUWE1, and HDAC1) in a protein–protein interaction (PPI) network consisting of 7 nodes and 11 edges. Compared with normal tissues, CLTC and TP53 genes were upregulated in stomach adenocarcinoma (P < 0.05). TP53 was expressed differently in stages II and IV, EWSR1 was expressed differently in stages II and III, and ESR1 was expressed differently in stages I–III. Among the seven hub genes, Kaplan–Meier analysis and TCGG showed that the expression levels of HDAC1 and CLTC were significantly correlated with OS in patients with stomach adenocarcinoma (P < 0.05). GEPIA2 analysis showed that ESR1 expression was closely correlated with OS and DFS in gastric adenocarcinoma (P < 0.05). Then, the expression of the genes and their correlations were revealed by the R2 Platform (http://r2.amc.nl). Finally, we collected 18 pairs of gastric mucosal tissues from normal people and cancer tissues from patients with stomach adenocarcinoma. The expression levels of the above seven hub genes and their relative protein expression were detected by RT-PCR and immunohistochemistry (IHC). The results showed that the gene and protein expression levels in stomach adenocarcinoma tissues were increased than those in the normal group.ConclusionIn summary, we believe that the identified hub genes were related to the occurrence of stomach adenocarcinoma, especially the expression of ESR1, HDAC1, and CLTC genes, which are related to the prognosis and overall survival of patients and may become the potential for the future diagnosis and treatment of STAD.

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Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes Associated With the Development of Stomach Adenocarcinoma by Integrated Bioinformatics Analysis

et al. 2022

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“…Interestingly, clathrin-heavy chain 1 (CLTC1) is an essential substance for the formation of membrane-invaginated vesicles and is involved in clathrin-independent endocytosis (CIE) and mitosis (Bond et al, 2018, Doherty andMcMahon, 2009). CLTC is associated with tumorigenesis, and Cheng Dongdong et al found that it is an important prognostic factor for OS patients and promotes tumor cell proliferation (Shijie et al, 2021). However, the molecular mechanism underlying OS needs further investigation.…”

Section: Umi-77 and Curcumin Synergistic Treating Osteosarcoma In Viv...mentioning

confidence: 99%

Integrated using UMI-77 and Curcumin Synergistic Treating Osteosarcoma by Targeting a Cuproptosis-Related Prognostic Model

Fu,

Wang,

Ren

et al. 2023

Preprint

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Background Among malignant bone sarcomas, osteosarcoma (OS) is the most frequent among young people. In recent studies, cuproptosis has been shown to play an important role in tumor progression. Evidence demonstrates that the combinatorial treatment with traditional Chinese medicine and western medicine improves the therapeutic effect on cancer, including OS. However, the combinatorial treatment targeting cuproptosis for OS remains elusive. Materials and Methods LASSO regression analysis was employed to establish and evaluate a cuproptosis-related prognostic model. The CIBERSORT algorithm was performed to demonstrate the significant differences in immune cell infiltration between low- and high-risk groups. Next, the CellMiner database was used to obtain potential drugs which target the risk score-related genes. Finally, we performed the network pharmacology and molecular docking studies to explore the combination of Chinese and western medicine on treatment of osteosarcoma. Results We found that the Chinese medicine, curcumin, and the western medicine, UMI-77 synergistic treating OS both in vivo and vitro. LASSO regression analysis was employed to establish and evaluate a cuproptosis-related prognostic model. Moreover, the CIBERSORT algorithm was performed to demonstrate the significant differences in immune cell infiltration between low- and high-risk groups. Notably, prognostic genes were related to 106 drugs obtained from the CellMiner database. Network pharmacology and molecular docking studies demonstrated that curcumin, the main active ingredient of curcumaelongae Rhizoma, targeted the suppressor gene, CLTC. Conclusion Our findings demonstrated that the combination of curcumin and UMI possess certain effect on osteosarcoma. And this study provides a theoretical framework for the integration of traditional Chinese medicine with western medicine for treating OS.

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“…In addition, NF-κB could combine with the regulatory sequence of the vimentin gene promoter to promote Twist expression and induce the EMT process [19,20]. The AKT/mTOR signaling pathway is frequently dysregulated in malignancies and plays a key role in numerous biological processes, including growth, proliferation, and survival [21,22]. Current research indicates that the AKT/mTOR pathway is critical for the malignant tumor EMT process [23,24].…”

Section: Introductionmentioning

confidence: 99%

NCAPG promotes proliferation of epithelial ovarian cancer by activating the NF-κB and AKT/mTOR pathways

Wang

Zhu

et al. 2022

Preprint

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Objective Dysregulation of nonstructural maintenance of chromosome condensin I complex subunit G (NCAPG) in ovarian cancer might be associated with tumor progression, while the mechanistic roles of NCAPG in epithelial ovarian cancer (EOC) are still unclear. In this research, we aimed to elucidate the potential role and molecular basis of NCAPG in EOC. Methods We identified differentially expressed genes (DEGs) between EOC and normal tissues based on five Gene Expression Omnibus (GEO) datasets (GSE18520, GSE54388, GSE9891, GSE63885 and GSE40595) and The Cancer Genome Atlas (TCGA) database. A protein–protein interaction (PPI) network was established to evaluate the relationship between the DEGs and to screen hub genes. The expression levels of the hub genes were further validated through the Human Protein Atlas (HPA) databases. Additionally, the prognostic values of the hub genes were evaluated by the Kaplan‒Meier plotter. Furthermore, the expression of NCAPG, the most remarkable hub gene in EOC, was examined by qRT‒PCR, immunohistochemistry (IHC), and western blotting. A2780 and SKOV3 cell lines were stably transfected with lentivirus to build knockdown and overexpression cell lines. CCK8, clone formation, transwell, and flow cytometry assays were used to evaluate the migratory and proliferation potential of EOC cells. Transcriptome profiling analysis was used to reveal the mechanism by which NCAPG regulated the epithelial-mesenchymal transition (EMT) of EOC. Finally, the mechanistic roles of NCAPG were examined through in vitro and in vivo experiments. Results Our findings demonstrated that NCAPG expression was enhanced in EOC tissues compared to normal ovarian tissues and was associated with poor prognosis. NCAPG could facilitate the proliferation, invasion, and migration of EOC cells through the EMT mechanism. Mechanistically, NCAPG could activate the NF-κB and AKT/mTOR pathways to regulate the EMT process of EOC. Conclusion Overall, our investigation revealed NCAPG as an important candidate oncogene in EOC. Targeting NCAPG could be a novel treatment with the potential to act as an EOC biomarker.

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Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF‐beta and AKT/mTOR signaling pathways

Cited by 9 publications

References 49 publications

Identification of Hub Genes Associated With the Development of Stomach Adenocarcinoma by Integrated Bioinformatics Analysis

Identification of Hub Genes Associated With the Development of Stomach Adenocarcinoma by Integrated Bioinformatics Analysis

Integrated using UMI-77 and Curcumin Synergistic Treating Osteosarcoma by Targeting a Cuproptosis-Related Prognostic Model

NCAPG promotes proliferation of epithelial ovarian cancer by activating the NF-κB and AKT/mTOR pathways

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