Title:FN1 Promotes Thyroid Carcinoma Cell Proliferation and Metastasis by
Activating the NF-Κb Pathway
Volume: 30
Issue: 1
Author(s): Chen Chen and Zhijun Shen*
Affiliation:
- Department of Clinical Laboratory, Hubei No.3 People’s Hospital of
Jianghan University, Wuhan 430033, Hubei, China
Keywords:
FN1, thyroid carcinoma, NF-κB, cell proliferation, metastasis, endocrine tumor.
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.
