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. 2023 Jul 9;13(1):11097.
doi: 10.1038/s41598-023-38158-x.

ZNF143 facilitates the growth and migration of glioma cells by regulating KPNA2-mediated Hippo signalling

Yan Chen #  1 , Jitao Li #  2 , Jiangchun Ma  3 , Yizhong Bao  4
Affiliations

ZNF143 facilitates the growth and migration of glioma cells by regulating KPNA2-mediated Hippo signalling

Yan Chen et al. Sci Rep. .

Abstract

The disordered expression of ZNF143 is closely related to the malignant progression of tumours. However, the basic control mechanism of ZNF143 in glioma has not yet been clarified. Therefore, we tried to find a new pathway to illustrate the function of ZNF143 in glioma. To explore the function of KPNA2 in the development of glioma, we used survival analysis by the Kaplan‒Meier method to assess the overall survival (OS) of patients with low and high KPNA2 expression in the TCGA and CGGA cohorts. Western blotting assays and RT‒PCR assays were utilized to determine the expression level of KPNA2 in glioma cells. The interaction between ZNF143 and KPNA2 was confirmed by ChIP assays. Proliferation was assessed by CCK-8 assays, and migration was evaluated by wound healing and Transwell assays. Apoptosis was determined by flow cytometry, and the expression level of YAP/TAZ was visualized using an immunofluorescence assay. The expression levels of LATS1, LATS2, YAP1, and p-YAP1 were determined. Patients with low KPNA2 expression showed a better prognosis than those with high KPNA2 expression. KPNA2 was found to be upregulated in human glioma cells. ZNF143 can bind to the promoter region of KPNA2. Downregulation of ZNF143 and KPNA2 can activate the Hippo signalling pathway and reduce YAP/TAZ expression in human glioma cells, thus inducing apoptosis of human glioma cells and weakening their proliferation, migration and invasion. In conclusion, ZNF143 mediates the Hippo/YAP signalling pathway and inhibits the growth and migration of glioma cells by regulating KPNA2.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Patients with low KPNA2 expression showed a better prognosis than those with high KPNA2 expression in both the TCGA and CGGA databases. KPNA2 was expressed in 33 types of malignant tumours compared to normal tissues (A); KPNA2 was expressed in glioma either in the TCGA database or CGGA database (B); Prognostic value of KPNA2 in glioma in the TCGA database or CGGA database (C).
Figure 2
Figure 2
The impact of KPNA2 on the proliferation, migration, and apoptosis of U373 cells. (A) The expression level of KPNA2 in U373 and NHA cells was determined by Western blotting and RT‒PCR (*p < 0.05 vs. NHA). (B) Cell viability was detected by CCK-8 assays. (C, D) Apoptosis was evaluated by flow cytometry. (E, F) The wound healing assay was utilized to determine the migration of U373 cells. (G, H) The migration of U373 cells was detected using the Transwell assay (*p < 0.05 vs. the control, # p < 0.05 vs. siRNA-NC).
Figure 3
Figure 3
The impact of KPNA2 on the YAP/TAZ pathway. (A, B) The expression level of YAP/TAZ in U373 cells was determined using immunofluorescence assays (*p < 0.05 vs. the control, #p < 0.05 vs. siRNA-NC). (C, D): The expression levels of LATS1, LATS2, YAP1, and p-YAP1 were determined using Western blotting (*p < 0.05 vs. the control, #p < 0.05 vs. siRNA-NC).
Figure 4
Figure 4
The interaction between ZNF143 and KPNA2 in glioma cells was confirmed using a ChIP assay. (A) The identification of the successful transfection of the KPNA2 overexpression vector (*p < 0.05 vs. the control). (B) A ChIP assays were utilized to demonstrate the interaction between ZNF143 and KPNA2 in glioma cells.
Figure 5
Figure 5
The impact of ZNF143 on the proliferation, migration, and apoptosis of U373 cells. (A) Cell viability was detected by CCK-8 assays. (B) Apoptosis was evaluated by flow cytometry. (C) The wound healing assay was utilized to determine the migration of U373 cells. (D) The migration of U373 cells was detected using the Transwell assay (*p < 0.05 vs. the control, # p < 0.05 vs. siRNA-NC).
Figure 6
Figure 6
The impact of ZNF143 on the YAP/TAZ pathway. (A, B) The expression level of YAP/TAZ in U373 cells was determined using the immunofluorescence assay (*p < 0.05 vs. the control, #p < 0.05 vs. siRNA-NC). (C–E) The expression level of KPNA2 in the ZNF143 knockdown U373 cells was evaluated by RT‒PCR and Western blotting assays (*p < 0.05 vs. the control, #p < 0.05 vs. siRNA-NC). (F, G) The expression levels of LATS1, LATS2, YAP1, and p-YAP1 were determined using Western blotting (*p < 0.05 vs. the control, #p < 0.05 vs. siRNA-NC).
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