FN1 Promotes Thyroid Carcinoma Cell Proliferation and Metastasis by Activating the NF-Κb Pathway.

IF 1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Protein and Peptide Letters Pub Date : 2023-01-01 DOI:10.2174/0929866530666221019162943

Chen Chen, Zhijun Shen

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引用次数: 3

Abstract

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.

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FN1通过激活NF-Κb通路促进甲状腺癌细胞的增殖和转移。

背景:甲状腺癌是一种常见的内分泌肿瘤。本研究旨在通过生物信息学方法鉴定thca相关关键基因Fibronectin 1 (FN1)，并探讨其功能和调控机制。方法:检索基因表达综合数据库(GSE3678、GSE33630和GSE53157数据集)，分析THCA组织与正常组织的差异表达基因(DEGs)。利用基因本体和京都基因与基因组百科全书路径数据库(DAVID)对deg的富集进行了研究。利用STRING数据库和Cytoscape软件筛选枢纽基因。利用基因表达谱交互分析数据库研究了这些中心基因在THCA中的表达和生存分析。在LinkedOmics数据库中搜索FN1在THCA中调控的相关信号通路。采用实时定量逆转录酶聚合酶链式反应检测纤维调节素、微纤维相关蛋白4、骨胰素、FN1 mRNA表达。采用细胞计数试剂盒- 8,5 -乙基-2 '-脱氧尿苷法、划痕法和Transwell法检测细胞的活力、生长、迁移和侵袭性。Western blot检测NF-κB信号通路相关蛋白(p- i -κB -α、p-IKK-β、NF-κB p65)的表达水平。结果:FN1 mRNA在THCA组织和细胞系(MDA-T85和MDA-T41)中表达上调。FN1的高表达与THCA患者肿瘤直径增大及淋巴结转移有关。功能实验表明，在MDA-T85细胞株中过表达FN1可促进生长、迁移和侵袭性;在MDA-T41细胞中敲低FN1抑制这些恶性行为。在机制上，FN1促进了NF-κB信号通路相关蛋白的表达水平，激活了NF-κB信号通路。结论:FN1在THCA中表达上调，通过激活NF-κB信号通路促进细胞生长、迁移和侵袭。FN1有望成为THCA的生物标志物，成为THCA治疗的分子靶点。

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来源期刊

Protein and Peptide Letters 生物-生化与分子生物学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

2 months

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