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. 2023 Nov 23;9(12):e22734.
doi: 10.1016/j.heliyon.2023.e22734. eCollection 2023 Dec.

FOXM1/KIF20A axis promotes clear cell renal cell carcinoma progression via regulating EMT signaling and affects immunotherapy response

Kai Fang  1 , Min Gong  1 , Dong Liu  1 , Shengjie Liang  1 , Yang Li  1 , Weicong Sang  1 , Rujian Zhu  1
Affiliations

FOXM1/KIF20A axis promotes clear cell renal cell carcinoma progression via regulating EMT signaling and affects immunotherapy response

Kai Fang et al. Heliyon. .

Abstract

Background: The correlation between FOXM1 and KIF20A has not been revealed in clear cell renal cell carcinoma (ccRCC).

Methods: Public data was downloaded from The Cancer Genome Atlas (TCGA) database. R software was utilized for the execution of bioinformatic analysis. The expression levels of specific molecules (mRNA and protein) were detected using real-time quantitative PCR (qRT-PCR) and Western blot assays. The capacity of cell growth was assessed by employing CCK8 and colony formation assay. Cell invasion and migration ability were assessed using transwell assay.

Results: In our study, we illustrated the association between FOXM1 and KIF20A. Our results indicated that both FOXM1 and KIF20A were associated with poor prognosis and clinical performance. The malignant characteristics of ccRCC cells can be significantly suppressed by inhibiting FOXM1 and KIF20A, as demonstrated by in vitro experiments. Moreover, we found that FOXM1 can upregulate KIF20A. Then, EMT signaling was identified as the underlying pathway FOXM1 and KIF20A are involved. WB results indicated that FOXM1/KIF20A axis can activate EMT signaling. Moreover, we noticed that FOXM1 and KIF20A can affect the immunotherapy response and immune microenvironment of ccRCC patients.

Conclusions: Our results identified the role of the FOXM1/KIF20A axis in ccRCC progression and immunotherapy, making it the underlying target for ccRCC.

Keywords: EMT; FOXM; Immunotherapy; KIF20A; ccRCC.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Expression pattern and clinical role of FOXM1 in ccRCC Notes: A: Expression level of FOXM1 in ccRCC and normal tissue; B: Expression level of FOXM1 in the paired ccRCC and normal tissue; C: Expression level of FOXM1 in different cell lines; D: KM curve of patients with high and low FOXM1 expression (OS); E: KM curve of patients with high and low FOXM1 expression (DSS); F: KM curve of patients with high and low FOXM1 expression (PFS); G: Expression level of FOXM1 in T1-2 and T3-4 patients; H: Expression level of FOXM1 in N0 and N1 patients; I: Expression level of FOXM1 in M0 and M1 patients.
Fig. 2
Fig. 2
FOXM1 promotes ccRCC proliferation, invasion and migration. Notes: A: qRT-PCR was used to detect the knockdown efficiency of FOXM1 in 786-O and Caki-1 cells; B–C: CCK8 assay was performed in the FOXM1 knockdown and control cells; D–E: Colony formtaion assay was performed in the FOXM1 knockdown and control cells; F–I: Transwell assay was performed in the FOXM1 knockdown and control cells.
Fig. 3
Fig. 3
Expression pattern and clinical role of KIF20A in ccRCC Notes: A: Correlation between FOXM1 and KIF20A in ccRCC; B: Expression level of KIF20A in the FOXM1 knockdown and control cells; C: Expression level of KIF20A in the ccRCC and normal tissue; D: KM curve of patients with high and low KIF20A expression (OS); E: KM curve of patients with high and low KIF20A expression (DSS); F: KM curve of patients with high and low KIF20A expression (PFS); G: Expression level of KIF20A in T1-2 and T3-4 patients; H: Expression level of KIF20A in N0 and N1 patients; I: Expression level of KIF20A in M0 and M1 patients.
Fig. 4
Fig. 4
KIF20A enhances the ccRCC malignant biological behaviors. Notes: A: qRT-PCR was used to detect the knockdown efficiency of KIF20A in 786-O and Caki-1 cells; B–C: CCK8 assay was performed in the KIF20A knockdown and control cells; D–E: Colony formation assay was performed in the KIF20A knockdown and control cells; F–I: Transwell assay was performed in the KIF20A knockdown and control cells.
Fig. 5
Fig. 5
FOXM1 promotes malignant phenotype by upregulating KIF20A. Notes: A: qRT-PCR was used to detect the overexpression efficiency of KIF20A in FOXM1 knockdown cells; B–C: CCK8 assay was performed in the sh#ctl, sh#FOXM1 and shFOXM1 + KIF20A-OE cells; D–E: Colony formation assay was performed in the sh#ctl, sh#FOXM1 and shFOXM1 + KIF20A-OE cells; F–H: Transwell assay was performed in the sh#ctl, sh#FOXM1 and shFOXM1 + KIF20A-OE cells.
Fig. 6
Fig. 6
FOXM1/KIF20A axis can affect the activity of EMT signaling. Notes: A: GSEA analysis of FOXM1 based on Hallmark gene set; B: GSEA analysis of KIF20A based on Hallmark gene set; C: WB assay was conducted to illustrate the effect of FOXM1 and KIF20A on EMT pathway.
Fig. 7
Fig. 7
FOXM1 and KIF20A can affect the immunotherapy response. Notes: A: TIDE algorithm was performed to quantify the immunotherapy response of ccRCC; B–C: The correlation between TIDE score and FOXM1, as well as KIF20A; D–E: The expression level of FOXM1 and KIF20A in the immunotherapy responders and non-responders; H–K: The correlation between KIF20A and key immune checkpoints; L–O: The correlation between FOXM1 and key immune checkpoints.
Fig. 8
Fig. 8
Effect of FOXM1 and KIF20A on ccRCC immune microenvironment and genome instability. Notes: A: The infiltration level of immune cells in patients with high and low KIF20A expression; B: The infiltration level of immune cells in patients with high and low FOXM1 expression; C: The correlation between KIF20A and TMB, as well as MSI; D: The correlation between FOXM1 and TMB, as well as MSI.
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