Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

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

Research Article

FOXN3 Expression Regulated by miR-299-5p Inhibiting the Proliferation, Migration and Invasion of Oral Squamous Cell Carcinoma Cells

Author(s): Kamilijiang Maimaitiming, Alimire Yilihamu, Kudusi Keyimu, Rexiati Keranmu, Jun Li, Hui Xu and Duolikun Wufuer*

Volume 29, Issue 9, 2022

Published on: 08 September, 2022

Page: [788 - 795] Pages: 8

DOI: 10.2174/0929866529666220816143538

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Oral squamous cell carcinoma (OSCC) is one of the commonest malignancies of the oral cavity. FOXN3 is a tumor suppressor that represses the progression of many tumors. Nonetheless, its role in OSCC has not been elucidated. This work is performed to probe the role and dysregulation mechanism of FOXN3 in OSCC.

Methods: FOXN3 mRNA and miR-299-5p expressions were quantified by quantitative real-time polymerase chain reaction (qRT-PCR); 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to detect OSCC cell growth; Transwell experiment was conducted to detect cell migration and invasion; dual-luciferase reporter experiment and bioinformatics were adopted to analyze the relationship between miR-299-5p and FOXN3; Western blot was implemented to detect FOXN3 protein expression.

Results: FOXN3 expression was remarkably down-modulated, and miR-299-5p expression was markedly up-modulated in OSCC tissues and cell lines compared with paracancerous tissues and normal oral epithelial cell line. FOXN3 overexpression impeded OSCC cell growth, migration and invasion. FOXN3 was proven to be a downstream target of miR-299-5p, and miR-299-5p mimics enhanced OSCC cell growth, migration and invasion. Moreover, FOXN3 overexpression partially reversed the promoting effects of miR-299-5p mimics on OSCC cell growth, migration and invasion.

Conclusion: FOXN3 expression is remarkably down-modulated in OSCC tissues and cell lines, and miR-299-5p targets FOXN3 to facilitate OSCC cell growth, migration and invasion. These results imply that miR-299-5p/FOXN3 axis may be a potential target for OSCC treatment.

Keywords: Oral squamous cell carcinoma, proliferation, metastasis, miR-299-5p, FOXN3, cell lines.

Graphical Abstract
[1]
Chai, A.W.Y.; Lim, K.P.; Cheong, S.C. Translational genomics and recent advances in oral squamous cell carcinoma. Semin. Cancer Biol., 2020, 61, 71-83.
[http://dx.doi.org/10.1016/j.semcancer.2019.09.011] [PMID: 31542510]
[2]
Ng, J.H.; Iyer, N.G.; Tan, M.H.; Edgren, G. Changing epidemiology of oral squamous cell carcinoma of the tongue: A global study. Head Neck, 2017, 39(2), 297-304.
[http://dx.doi.org/10.1002/hed.24589] [PMID: 27696557]
[3]
Brands, M.T.; Brennan, P.A.; Verbeek, A.L.M.; Merkx, M.A.W.; Geurts, S.M.E. Follow-up after curative treatment for oral squamous cell carcinoma. A critical appraisal of the guidelines and a review of the literature. Eur. J. Surg. Oncol., 2018, 44(5), 559-565.
[http://dx.doi.org/10.1016/j.ejso.2018.01.004] [PMID: 29433990]
[4]
Balciunaite, G.; Keller, M.P.; Balciunaite, E.; Piali, L.; Zuklys, S.; Mathieu, Y.D.; Gill, J.; Boyd, R.; Sussman, D.J.; Holländer, G.A. Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat. Immunol., 2002, 3(11), 1102-1108.
[http://dx.doi.org/10.1038/ni850] [PMID: 12379851]
[5]
Xue, W.; Ma, L.; Wang, Z.; Zhang, W.; Zhang, X. FOXN3 is downregulated in osteosarcoma and transcriptionally regulates SIRT6, and suppresses migration and invasion in osteosarcoma. Oncol. Rep., 2019, 41(2), 1404-1414.
[PMID: 30483801]
[6]
Dai, Y.; Wang, M.; Wu, H.; Xiao, M.; Liu, H.; Zhang, D. Loss of FOXN3 in colon cancer activates beta-catenin/TCF signaling and promotes the growth and migration of cancer cells. Oncotarget, 2017, 8(6), 9783-9793.
[http://dx.doi.org/10.18632/oncotarget.14189] [PMID: 28039460]
[7]
Peng, Q.; Zhang, L.; Li, J.; Wang, W.; Cai, J.; Ban, Y.; Zhou, Y.; Hu, M.; Mei, Y.; Zeng, Z.; Li, X.; Xiong, W.; Li, G.; Tan, Y.; Xiang, B.; Yi, M. FOXA1 suppresses the growth, migration, and invasion of nasopharyngeal carcinoma cells through repressing miR-100-5p and miR-125b-5p. J. Cancer, 2020, 11(9), 2485-2495.
[http://dx.doi.org/10.7150/jca.40709] [PMID: 32201519]
[8]
Ding, N.; Luo, M.; Liao, X.L.; Bao, Q.Y.; Li, R.Y.; Wu, B. MicroRNA-378 promotes the malignant progression of oral squamous cell carcinoma by mediating FOXN3. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(14), 6202-6210.
[PMID: 31364120]
[9]
Berindan-Neagoe, I. Monroig, Pdel.C.; Pasculli, B.; Calin, G.A. MicroRNAome genome: A treasure for cancer diagnosis and therapy. CA Cancer J. Clin., 2014, 64(5), 311-336.
[http://dx.doi.org/10.3322/caac.21244] [PMID: 25104502]
[10]
He, B.; Lin, X.; Tian, F.; Yu, W.; Qiao, B. MiR-133a-3p inhibits Oral Squamous Cell Carcinoma (OSCC) proliferation and invasion by suppressing COL1A1. J. Cell. Biochem., 2018, 119(1), 338-346.
[http://dx.doi.org/10.1002/jcb.26182] [PMID: 28569392]
[11]
Chen, Y.H.; Song, Y.; Yu, Y.L.; Cheng, W.; Tong, X. miRNA-10a promotes cancer cell proliferation in oral squamous cell carcinoma by upregulating GLUT1 and promoting glucose metabolism. Oncol. Lett., 2019, 17(6), 5441-5446.
[http://dx.doi.org/10.3892/ol.2019.10257] [PMID: 31186763]
[12]
Yang, J.; Wang, H.; Xu, W.; Chen, Z.; Yan, Z.Y.; Zhang, L.J. Inhibition of miR-133b indicates poor prognosis and promotes progression of OSCC via SOX4. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(24), 12717-12726.
[PMID: 33378019]
[13]
Jiang, X.; Shen, X. Knockdown of miR-299-5p inhibits the progression of hepatocellular carcinoma by targeting SIAH1. Bull. Cancer, 2018, 105(10), 873-883.
[http://dx.doi.org/10.1016/j.bulcan.2018.07.013] [PMID: 30266288]
[14]
Zhang, C.L.; Li, L.B.; She, C.; Xie, Y.; Ge, D.W.; Dong, Q.R. MiR-299-5p targets cell cycle to promote cell proliferation and progression of osteosarcoma. Eur. Rev. Med. Pharmacol. Sci., 2018, 22(9), 2606-2613.
[PMID: 29771409]
[15]
Azarbarzin, S.; Hosseinpour Feizi, M.A.; Safaralizadeh, R.; Ravanbakhsh, R.; Kazemzadeh, M.; Fateh, A.; Karimi, N.; Moaddab, Y. The value of miR-299-5p in diagnosis and prognosis of intestinal-type gastric adenocarcinoma. Biochem. Genet., 2016, 54(4), 413-420.
[http://dx.doi.org/10.1007/s10528-016-9728-y] [PMID: 27007598]
[16]
Smyth, E.C.; Lagergren, J.; Fitzgerald, R.C.; Lordick, F.; Shah, M.A.; Lagergren, P.; Cunningham, D. Oesophageal cancer. Nat. Rev. Dis. Primers, 2017, 3, 17048.
[http://dx.doi.org/10.1038/nrdp.2017.48] [PMID: 28748917]
[17]
Karanth, S.; Adams, J.D.; Serrano, M.L.A.; Quittner-Strom, E.B.; Simcox, J.; Villanueva, C.J.; Ozcan, L.; Holland, W.L.; Yost, H.J.; Vella, A.; Schlegel, A. A Hepatocyte FOXN3-α cell glucagon axis regulates fasting glucose. Cell Rep., 2018, 24(2), 312-319.
[http://dx.doi.org/10.1016/j.celrep.2018.06.039] [PMID: 29996093]
[18]
Karanth, S.; Zinkhan, E.K.; Hill, J.T.; Yost, H.J.; Schlegel, A. FOXN3 regulates hepatic glucose utilization. Cell Rep., 2016, 15(12), 2745-2755.
[http://dx.doi.org/10.1016/j.celrep.2016.05.056] [PMID: 27292639]
[19]
Kong, X.; Zhai, J.; Yan, C.; Song, Y.; Wang, J.; Bai, X.; Brown, J.A.L.; Fang, Y. Recent advances in understanding FOXN3 in breast cancer, and other malignancies. Front. Oncol., 2019, 9, 234.
[http://dx.doi.org/10.3389/fonc.2019.00234] [PMID: 31214487]
[20]
Zhao, C.; Mo, L.; Li, C.; Han, S.; Zhao, W.; Liu, L. FOXN3 suppresses the growth and invasion of papillary thyroid cancer through the inactivation of Wnt/β-catenin pathway. Mol. Cell. Endocrinol., 2020, 515, 110925.
[http://dx.doi.org/10.1016/j.mce.2020.110925] [PMID: 32619584]
[21]
Chen, S.; Zhang, J.; Sun, L.; Li, X.; Bai, J.; Zhang, H.; Li, T. miR-611 promotes the proliferation, migration and invasion of tongue squamous cell carcinoma cells by targeting FOXN3. Oral Dis., 2019, 25(8), 1906-1918.
[http://dx.doi.org/10.1111/odi.13177] [PMID: 31419344]
[22]
Maatouk, D.; Harfe, B. MicroRNAs in development. ScientificWorldJournal, 2006, 6, 1828-1840.
[http://dx.doi.org/10.1100/tsw.2006.313] [PMID: 17205190]
[23]
Lu, T.X.; Rothenberg, M.E. MicroRNA. J. Allergy Clin. Immunol., 2018, 141(4), 1202-1207.
[http://dx.doi.org/10.1016/j.jaci.2017.08.034] [PMID: 29074454]
[24]
Mishra, S.; Yadav, T.; Rani, V. Exploring miRNA based approaches in cancer diagnostics and therapeutics. Crit. Rev. Oncol. Hematol., 2016, 98, 12-23.
[http://dx.doi.org/10.1016/j.critrevonc.2015.10.003] [PMID: 26481951]
[25]
Li, C.; Wang, A.; Chen, Y.; Liu, Y.; Zhang, H.; Zhou, J. MicroRNA2995p inhibits cell metastasis in breast cancer by directly targeting serine/threonine kinase 39. Oncol. Rep., 2020, 43(4), 1221-1233.
[PMID: 32020227]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy