{"title":"FN1通过激活NF-Κb通路促进甲状腺癌细胞的增殖和转移。","authors":"Chen Chen, Zhijun Shen","doi":"10.2174/0929866530666221019162943","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Thyroid cancer (THCA) is a common endocrine tumor. This study aims to identify the THCA-related key gene Fibronectin 1 (FN1) by bioinformatics methods and explore its function and regulatory mechanism.</p><p><strong>Methods: </strong>Gene Expression Omnibus database (GSE3678, GSE33630, and GSE53157 datasets) was searched for the analysis of differentially expressed genes (DEGs) in THCA tissues v.s. (normal tissues). The enrichment of DEGs was investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways using the DAVID database. Screening the hub gene was performed with the STRING database and Cytoscape software. The expression and survival analyses of these hub genes in THCA were studied with the Gene Expression Profiling Interactive Analysis database. LinkedOmics database was searched for the related signaling pathways regulated by FN1 in THCA. Real-time quantitative reverse transcriptase polymerase chain reaction was adopted to detect the mRNA expression of Fibromodulin, microfibril-associated protein 4, Osteoglycin, and FN1. The cell viability, growth, migration and aggressiveness were examined by Cell counting kit-8, 5-Ethynyl-2 '- deoxyuridine assay, scratch assay, and Transwell assay. The expression levels of NF-κB signaling pathway-related proteins (p-IκB-α, p-IKK-β, NF-κB p65) were detected by Western blot.</p><p><strong>Results: </strong>FN1 mRNA was up-regulated in THCA tissues and cell lines (MDA-T85 and MDA-T41). The high expression of FN1 is relevant to larger tumor diameters and lymph node metastasis in sufferers with THCA. Functional experiments showed that overexpression of FN1 in the MDA-T85 cell line promoted growth, migration and aggressiveness; knockdown of FN1 in MDA-T41 cells inhibited these malignant behaviors. In mechanism, FN1 promoted the expression levels of proteins related with NF-κB signaling pathway and activated NF-κB signaling pathway.</p><p><strong>Conclusion: </strong>FN1 is up-regulated in THCA and facilitates cell growth, migration and invasion by activating the NF-κB signaling pathway. FN1 will be a promising biomarker of THCA and may become a molecular target for THCA treatment.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"30 1","pages":"54-64"},"PeriodicalIF":1.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"FN1 Promotes Thyroid Carcinoma Cell Proliferation and Metastasis by Activating the NF-Κb Pathway.\",\"authors\":\"Chen Chen, Zhijun Shen\",\"doi\":\"10.2174/0929866530666221019162943\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Thyroid cancer (THCA) is a common endocrine tumor. This study aims to identify the THCA-related key gene Fibronectin 1 (FN1) by bioinformatics methods and explore its function and regulatory mechanism.</p><p><strong>Methods: </strong>Gene Expression Omnibus database (GSE3678, GSE33630, and GSE53157 datasets) was searched for the analysis of differentially expressed genes (DEGs) in THCA tissues v.s. (normal tissues). The enrichment of DEGs was investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways using the DAVID database. Screening the hub gene was performed with the STRING database and Cytoscape software. The expression and survival analyses of these hub genes in THCA were studied with the Gene Expression Profiling Interactive Analysis database. LinkedOmics database was searched for the related signaling pathways regulated by FN1 in THCA. Real-time quantitative reverse transcriptase polymerase chain reaction was adopted to detect the mRNA expression of Fibromodulin, microfibril-associated protein 4, Osteoglycin, and FN1. The cell viability, growth, migration and aggressiveness were examined by Cell counting kit-8, 5-Ethynyl-2 '- deoxyuridine assay, scratch assay, and Transwell assay. The expression levels of NF-κB signaling pathway-related proteins (p-IκB-α, p-IKK-β, NF-κB p65) were detected by Western blot.</p><p><strong>Results: </strong>FN1 mRNA was up-regulated in THCA tissues and cell lines (MDA-T85 and MDA-T41). The high expression of FN1 is relevant to larger tumor diameters and lymph node metastasis in sufferers with THCA. Functional experiments showed that overexpression of FN1 in the MDA-T85 cell line promoted growth, migration and aggressiveness; knockdown of FN1 in MDA-T41 cells inhibited these malignant behaviors. In mechanism, FN1 promoted the expression levels of proteins related with NF-κB signaling pathway and activated NF-κB signaling pathway.</p><p><strong>Conclusion: </strong>FN1 is up-regulated in THCA and facilitates cell growth, migration and invasion by activating the NF-κB signaling pathway. FN1 will be a promising biomarker of THCA and may become a molecular target for THCA treatment.</p>\",\"PeriodicalId\":20736,\"journal\":{\"name\":\"Protein and Peptide Letters\",\"volume\":\"30 1\",\"pages\":\"54-64\"},\"PeriodicalIF\":1.0000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Protein and Peptide Letters\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.2174/0929866530666221019162943\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Protein and Peptide Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.2174/0929866530666221019162943","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
FN1 Promotes Thyroid Carcinoma Cell Proliferation and Metastasis by Activating the NF-Κb Pathway.
Background: Thyroid cancer (THCA) is a common endocrine tumor. This study aims to identify the THCA-related key gene Fibronectin 1 (FN1) by bioinformatics methods and explore its function and regulatory mechanism.
Methods: Gene Expression Omnibus database (GSE3678, GSE33630, and GSE53157 datasets) was searched for the analysis of differentially expressed genes (DEGs) in THCA tissues v.s. (normal tissues). The enrichment of DEGs was investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways using the DAVID database. Screening the hub gene was performed with the STRING database and Cytoscape software. The expression and survival analyses of these hub genes in THCA were studied with the Gene Expression Profiling Interactive Analysis database. LinkedOmics database was searched for the related signaling pathways regulated by FN1 in THCA. Real-time quantitative reverse transcriptase polymerase chain reaction was adopted to detect the mRNA expression of Fibromodulin, microfibril-associated protein 4, Osteoglycin, and FN1. The cell viability, growth, migration and aggressiveness were examined by Cell counting kit-8, 5-Ethynyl-2 '- deoxyuridine assay, scratch assay, and Transwell assay. The expression levels of NF-κB signaling pathway-related proteins (p-IκB-α, p-IKK-β, NF-κB p65) were detected by Western blot.
Results: FN1 mRNA was up-regulated in THCA tissues and cell lines (MDA-T85 and MDA-T41). The high expression of FN1 is relevant to larger tumor diameters and lymph node metastasis in sufferers with THCA. Functional experiments showed that overexpression of FN1 in the MDA-T85 cell line promoted growth, migration and aggressiveness; knockdown of FN1 in MDA-T41 cells inhibited these malignant behaviors. In mechanism, FN1 promoted the expression levels of proteins related with NF-κB signaling pathway and activated NF-κB signaling pathway.
Conclusion: FN1 is up-regulated in THCA and facilitates cell growth, migration and invasion by activating the NF-κB signaling pathway. FN1 will be a promising biomarker of THCA and may become a molecular target for THCA treatment.
期刊介绍：
Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations.
Protein & Peptide Letters focuses on:
Structure Studies
Advances in Recombinant Expression
Drug Design
Chemical Synthesis
Function
Pharmacology
Enzymology
Conformational Analysis
Immunology
Biotechnology
Protein Engineering
Protein Folding
Sequencing
Molecular Recognition
Purification and Analysis
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
