Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Chen Chen and Zhijun Shen*

Volume 30, Issue 1, 2023

Published on: 30 November, 2022

Page: [54 - 64] Pages: 11

DOI: 10.2174/0929866530666221019162943

Price: $65

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.

Keywords: FN1, thyroid carcinoma, NF-κB, cell proliferation, metastasis, endocrine tumor.

« Previous Next »
Graphical Abstract

[1]
Zaballos, M.A.; Santisteban, P. Key signaling pathways in thyroid cancer. J. Endocrinol., 2017, 235(2), R43-R61.
[http://dx.doi.org/10.1530/JOE-17-0266] [PMID: 28838947]
[2]
Aschebrook-Kilfoy, B.; Ward, M.H.; Sabra, M.M.; Devesa, S.S. Thyroid cancer incidence patterns in the United States by histologic type, 1992-2006. Thyroid, 2011, 21(2), 125-134.
[http://dx.doi.org/10.1089/thy.2010.0021] [PMID: 21186939]
[3]
Qiu, Z.; Li, H.; Wang, J.; Sun, C. miR-146a and miR-146b in the diagnosis and prognosis of papillary thyroid carcinoma. Oncol. Rep., 2017, 38(5), 2735-2740.
[http://dx.doi.org/10.3892/or.2017.5994] [PMID: 29048684]
[4]
Kunavisarut, T. Diagnostic biomarkers of differentiated thyroid cancer. Endocrine, 2013, 44(3), 616-622.
[http://dx.doi.org/10.1007/s12020-013-9974-2] [PMID: 23645523]
[5]
Ji, F.; Sadreyev, R.I. RNA-seq: Basic bioinformatics analysis. Curr. Protoc. Mol. Biol., 2018, 124(1), e68.
[http://dx.doi.org/10.1002/cpmb.68] [PMID: 30222249]
[6]
Chen, C.; Hou, J.; Tanner, J.J.; Cheng, J. Bioinformatics methods for mass spectrometry-based proteomics data analysis. Int. J. Mol. Sci., 2020, 21(8), 2873.
[http://dx.doi.org/10.3390/ijms21082873] [PMID: 32326049]
[7]
Wan, Y.; Zhang, X.; Leng, H.; Yin, W.; Zeng, W.; Zhang, C. Identifying hub genes of papillary thyroid carcinoma in the TCGA and GEO database using bioinformatics analysis. PeerJ, 2020, 8, e9120.
[http://dx.doi.org/10.7717/peerj.9120] [PMID: 32714651]
[8]
Wang, S.; Wu, J.; Guo, C.; Shang, H.; Yao, J.; Liao, L.; Dong, J. Identification and validation of novel genes in anaplastic thyroid carcinoma via bioinformatics analysis. Cancer Manag. Res., 2020, 12, 9787-9799.
[http://dx.doi.org/10.2147/CMAR.S250792] [PMID: 33116838]
[9]
Hu, S.; Liao, Y.; Chen, L. Identification of key pathways and genes in anaplastic thyroid carcinoma via integrated bioinformatics analysis. Med. Sci. Monit., 2018, 24, 6438-6448.
[http://dx.doi.org/10.12659/MSM.910088] [PMID: 30213925]
[10]
Liebner, D.A.; Shah, M.H. Thyroid cancer: pathogenesis and targeted therapy. Ther. Adv. Endocrinol. Metab., 2011, 2(5), 173-195.
[http://dx.doi.org/10.1177/2042018811419889] [PMID: 23148184]
[11]
Pusztaszeri, M.; Auger, M. Update on the cytologic features of papillary thyroid carcinoma variants. Diagn. Cytopathol., 2017, 45(8), 714-730.
[http://dx.doi.org/10.1002/dc.23703] [PMID: 28262004]
[12]
Liu, Y.; Gao, S.; Jin, Y.; Yang, Y.; Tai, J.; Wang, S.; Yang, H.; Chu, P.; Han, S.; Lu, J.; Ni, X.; Yu, Y.; Guo, Y. Bioinformatics analysis to screen key genes in papillary thyroid carcinoma. Oncol. Lett., 2020, 19(1), 195-204.
[PMID: 31897130]
[13]
Ye, Y.; Zhuang, J.; Wang, G.; He, S.; Ni, J.; Xia, W. MicroRNA 139 targets fibronectin 1 to inhibit papillary thyroid carcinoma progression. Oncol. Lett., 2017, 14(6), 7799-7806.
[http://dx.doi.org/10.3892/ol.2017.7201] [PMID: 29250177]
[14]
Cao, M.; Xiao, D.; Ding, X. The anti-tumor effect of ursolic acid on papillary thyroid carcinoma via suppressing Fibronectin-1. Biosci. Biotechnol. Biochem., 2020, 84(12), 2415-2424.
[http://dx.doi.org/10.1080/09168451.2020.1813543] [PMID: 32942951]
[15]
Sponziello, M.; Rosignolo, F.; Celano, M.; Maggisano, V.; Pecce, V.; De Rose, R.F.; Lombardo, G.E.; Durante, C.; Filetti, S.; Damante, G.; Russo, D.; Bulotta, S. Fibronectin-1 expression is increased in aggressive thyroid cancer and favors the migration and invasion of cancer cells. Mol. Cell. Endocrinol., 2016, 431, 123-132.
[http://dx.doi.org/10.1016/j.mce.2016.05.007] [PMID: 27173027]
[16]
Liu, C.; Feng, Z.; Chen, T.; Lv, J.; Liu, P.; Jia, L.; Zhu, J.; Chen, F.; Yang, C.; Deng, Z. Retracted Article: Downregulation of NEAT1 reverses the radioactive iodine resistance of papillary thyroid carcinoma cell via miR-101-3p/FN1/PI3K-AKT signaling pathway. Cell Cycle, 2019, 18(2), 167-203.
[http://dx.doi.org/10.1080/15384101.2018.1560203] [PMID: 30596336]
[17]
Karin, M. Nuclear factor-κB in cancer development and progression. Nature, 2006, 441(7092), 431-436.
[http://dx.doi.org/10.1038/nature04870] [PMID: 16724054]
[18]
Pozdeyev, N.; Berlinberg, A.; Zhou, Q.; Wuensch, K.; Shibata, H.; Wood, W.M.; Haugen, B.R. Targeting the NF-κB pathway as a combination therapy for advanced thyroid cancer. PLoS One, 2015, 10(8), e0134901.
[http://dx.doi.org/10.1371/journal.pone.0134901] [PMID: 26263379]
[19]
Ma, Y.; Wang, Q.; Liu, F.; Ma, X.; Wu, L.; Guo, F.; Zhao, S.; Huang, F.; Qin, G. KLF5 promotes the tumorigenesis and metastatic potential of thyroid cancer cells through the NF-κB signaling pathway. Oncol. Rep., 2018, 40(5), 2608-2618.
[http://dx.doi.org/10.3892/or.2018.6687] [PMID: 30226614]
[20]
Gao, Y.; Elamin, E.; Zhou, R.; Yan, H.; Liu, S.; Hu, S.; Dong, J.; Wei, M.; Sun, L.; Zhao, Y. FKBP51 promotes migration and invasion of papillary thyroid carcinoma through NF-κB-dependent epithelial-to-mesenchymal transition. Oncol. Lett., 2018, 16(6), 7020-7028.
[http://dx.doi.org/10.3892/ol.2018.9517] [PMID: 30546435]
[21]
Zhao, S.; Wang, Q.; Li, Z.; Ma, X.; Wu, L.; Ji, H.; Qin, G. LDOC1 inhibits proliferation and promotes apoptosis by repressing NF-κB activation in papillary thyroid carcinoma. J. Exp. Clin. Cancer Res., 2015, 34(1), 146.
[http://dx.doi.org/10.1186/s13046-015-0265-z] [PMID: 26637328]
[22]
Wang, J.; Deng, L.; Huang, J.; Cai, R.; Zhu, X.; Liu, F.; Wang, Q.; Zhang, J.; Zheng, Y. High expression of Fibronectin 1 suppresses apoptosis through the NF-κB pathway and is associated with migration in nasopharyngeal carcinoma. Am. J. Transl. Res., 2017, 9(10), 4502-4511.
[PMID: 29118912]
[23]
Uetaki, M.; Onishi, N.; Oki, Y.; Shimizu, T.; Sugihara, E.; Sampetrean, O.; Watanabe, T.; Yanagi, H.; Suda, K.; Fujii, H.; Kano, K.; Saya, H.; Nobusue, H. Regulatory roles of fibronectin and integrin α5 in reorganization of the actin cytoskeleton and completion of adipogenesis. Mol. Biol. Cell, 2022, 33(9), ar78.
[http://dx.doi.org/10.1091/mbc.E21-12-0609] [PMID: 35704469]
[24]
Titus, A.S.; Venugopal, H.; Ushakumary, M.G.; Wang, M.; Cowling, R.T.; Lakatta, E.G.; Kailasam, S. Discoidin domain receptor 2 Regulates AT1R expression in angiotensin ii-stimulated cardiac fibroblasts via fibronectin-dependent integrin-β1 signaling. Int. J. Mol. Sci., 2021, 22(17), 9343.
[http://dx.doi.org/10.3390/ijms22179343] [PMID: 34502259]
[25]
Zhou, X.; Zhai, Y.; Liu, C.; Yang, G.; Guo, J.; Li, G.; Sun, C.; Qi, X.; Li, X.; Guan, F. Sialidase NEU1 suppresses progression of human bladder cancer cells by inhibiting fibronectin-integrin α5β1 interaction and Akt signaling pathway. Cell Commun. Signal., 2020, 18(1), 44.
[http://dx.doi.org/10.1186/s12964-019-0500-x] [PMID: 32164705]

Rights & Permissions Print Cite
Article Metrics
34
1
© 2024 Bentham Science Publishers | Privacy Policy