Role of FOXM1 and AURKB in Regulating Keratinocyte Function in Psoriasis

Overview

Journal Open Med (Wars)

Specialty General Medicine

Date 2024 Oct 9

PMID 39381423

Authors

Zhaofeng Zhao

Jie Cheng

Qiang Hou

Jian Zhu

Tu Chen

Sheng Lu

Guiju Wu

Hongli Lv

Xiujuan Wu

Affiliations

Soon will be listed here.

Abstract

Objective: This study investigated the effect of forkhead box M1 (FOXM1) and Aurora kinase B (AURKB) on the epidermal function of keratinocytes.

Methods: Bioinformatics analysis was used to analyze the co-expression network of FOXM1 and its correlation with AURKB. The expression of FOXM1 and AURKB in tissues and cells was detected by immunofluorescence and real-time quantitative polymerase chain reaction, respectively. HaCaT cells were transfected with si-FOXM1 to knock down FOXM1. Cell proliferation was detected by cell counting kit-8 assay. Cell migration was detected by scratch assay. Cell invasion was detected by the Transwell invasion assay. Cell apoptosis and cell cycle were detected by flow cytometry.

Results: FOXM1 and AURKB were positively correlated and highly expressed in psoriatic lesions. After transfection of si-FOXM1, the expression levels of FOXM1 and AURKB genes significantly decreased. The proliferation of HaCaT cells decreased, the apoptosis rate increased significantly, and the proportion of cells in the G1 phase increased significantly, while the proportion of cells in the S phase decreased significantly. The scratch closure of HaCaT cells was reduced, and the number of cell invasions decreased significantly.

Conclusion: FOXM1 and AURKB may affect the progression of psoriasis by regulating the proliferation, cell cycle, migration, and invasion of keratinocytes.

References

Hu Y, Shen F, Crellin N, Ouyang W . The IL-17 pathway as a major therapeutic target in autoimmune diseases. Ann N Y Acad Sci. 2010; 1217:60-76. DOI: 10.1111/j.1749-6632.2010.05825.x. View

Zhao Z, Cheng J, Sun W, Zhu J, Lu S, Feng Y . The LINC01176-miR-218-5p-IL-36G Network is Responsible for the Pathogenesis of Psoriasis by Promoting Inflammation. Clin Cosmet Investig Dermatol. 2024; 17:1-12. PMC: 10771785. DOI: 10.2147/CCID.S444265. View

Tang H, Tang X, Guo Z, Cheng H, Zheng X, Chen G . AURKA facilitates the psoriasis-related inflammation by impeding autophagy-mediated AIM2 inflammasome suppression. Immunol Lett. 2021; 240:98-105. DOI: 10.1016/j.imlet.2021.10.004. View

Bella L, Zona S, Nestal de Moraes G, Lam E . FOXM1: A key oncofoetal transcription factor in health and disease. Semin Cancer Biol. 2014; 29:32-9. DOI: 10.1016/j.semcancer.2014.07.008. View

Wang I, Chen Y, Hughes D, Petrovic V, Major M, Park H . Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase. Mol Cell Biol. 2005; 25(24):10875-94. PMC: 1316960. DOI: 10.1128/MCB.25.24.10875-10894.2005. View

Zhang Z, Li M, Sun T, Zhang Z, Liu C . FOXM1: Functional Roles of FOXM1 in Non-Malignant Diseases. Biomolecules. 2023; 13(5). PMC: 10216727. DOI: 10.3390/biom13050857. View

Griffiths C, Armstrong A, Gudjonsson J, Barker J . Psoriasis. Lancet. 2021; 397(10281):1301-1315. DOI: 10.1016/S0140-6736(20)32549-6. View

Zhao J, Wang F, Tian Q, Dong J, Chen L, Hu R . Involvement of miR-214-3p/FOXM1 Axis During the Progression of Psoriasis. Inflammation. 2021; 45(1):267-278. DOI: 10.1007/s10753-021-01544-6. View

Borhani S, Gartel A . FOXM1: a potential therapeutic target in human solid cancers. Expert Opin Ther Targets. 2020; 24(3):205-217. DOI: 10.1080/14728222.2020.1727888. View

10.

Lowes M, Suarez-Farinas M, Krueger J . Immunology of psoriasis. Annu Rev Immunol. 2014; 32:227-55. PMC: 4229247. DOI: 10.1146/annurev-immunol-032713-120225. View

11.

Luo Y, Ding X, Du H, Wu Y, Li H, Wu H . FOXM1 is a novel predictor of recurrence in patients with oral squamous cell carcinoma associated with an increase in epithelial‑mesenchymal transition. Mol Med Rep. 2019; 19(5):4101-4108. PMC: 6471394. DOI: 10.3892/mmr.2019.10094. View

12.

Zhang Z, Xue S, Gao Y, Li Y, Zhou Z, Wang J . Small molecule targeting FOXM1 DNA binding domain exhibits anti-tumor activity in ovarian cancer. Cell Death Discov. 2022; 8(1):280. PMC: 9184618. DOI: 10.1038/s41420-022-01070-w. View

13.

Nigg E . Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol. 2001; 2(1):21-32. DOI: 10.1038/35048096. View

14.

Rendon A, Schakel K . Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019; 20(6). PMC: 6471628. DOI: 10.3390/ijms20061475. View

15.

Nie M, Wang Y, Yu Z, Li X, Deng Y, Wang Y . AURKB promotes gastric cancer progression via activation of expression. Aging (Albany NY). 2020; 12(2):1304-1321. PMC: 7053608. DOI: 10.18632/aging.102684. View

16.

Hu G, Yan Z, Zhang C, Cheng M, Yan Y, Wang Y . FOXM1 promotes hepatocellular carcinoma progression by regulating KIF4A expression. J Exp Clin Cancer Res. 2019; 38(1):188. PMC: 6507024. DOI: 10.1186/s13046-019-1202-3. View

17.

Lowes M, Russell C, Martin D, Towne J, Krueger J . The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol. 2013; 34(4):174-81. PMC: 3721313. DOI: 10.1016/j.it.2012.11.005. View

18.

Kelleher F, OSullivan H . FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways. Oncotarget. 2016; 7(27):42792-42804. PMC: 5173172. DOI: 10.18632/oncotarget.8669. View

19.

Madhi H, Lee J, Choi Y, Li Y, Kim M, Choi Y . FOXM1 Inhibition Enhances the Therapeutic Outcome of Lung Cancer Immunotherapy by Modulating PD-L1 Expression and Cell Proliferation. Adv Sci (Weinh). 2022; 9(29):e2202702. PMC: 9561767. DOI: 10.1002/advs.202202702. View

20.

Molinuevo R, Freije A, de Pedro I, Stoll S, Elder J, Gandarillas A . FOXM1 allows human keratinocytes to bypass the oncogene-induced differentiation checkpoint in response to gain of MYC or loss of p53. Oncogene. 2016; 36(7):956-965. PMC: 5318665. DOI: 10.1038/onc.2016.262. View