ZDHHC12 regulates tumor properties through YAP1 in glioblastoma

doi:10.19401/j.cnki.1007-3639.2022.06.007

Abstract

Abstract:

Background and purpose: Glioblastoma (GBM) is one of the most malignant brain tumors, however, the pathogenesis of GBM has not been thoroughly studied. The purpose of this study was to analyze the regulation of Yes-associated protein 1 (YAP1) by zinc finger DHHC domain-containing protein 12 (ZDHHC12), and the regulation of GBM tumor characteristics through the ZDHHC12/YAP1 axis. Methods: The expression of ZDHHC12 in normal brain tissue and GBM was analyzed in the The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) database. Western blot and real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) were used to detect the mRNA expression and protein levels in U87, U251 and NHA. ZDHHC12 was knocked down by designed siRNA in two GBM cell lines, U87 and U251, and the protein levels of YAP1 were detected. The interaction between endogenous and exogenous ZDHHC12 and YAP1 was verified by co-immunoprecipitation (Co-IP). The changes in proliferation and migration ability of GBM cells after knockdown of ZDHHC12 and restoration of YAP1 were analyzed by cell counting kit-8 (CCK-8) assay, cell plate clone formation assay and scratch assay. Changes in markers of epithelial-mesenchymal transition (EMT) in GBM cell lines after knockdown of ZDHHC12 and restoration of YAP1 were detected. The effect of ZDHHC12 on the prognosis of GBM patients was analyzed, and detection of the protein levels of ZDHHC12 and YAP1 in different tissue samples was carried out. Results: The analysis results of TCGA database and GTEx database showed that the expression of ZDHHC12 was significantly higher in GBM than in normal brain tissue (P<0.01), and the mRNA and protein levels of ZDHHC12 were higher in GBM cell lines than in NHAs cell lines. Knockdown of ZDHHC12 in both U87 and U251 GBM cell lines caused a decrease in YAP1 protein levels. Co-IP experiments verified the interaction between ZDHHC12 and YAP1 proteins. Knockdown of ZDHHC12 could significantly inhibit the proliferation and migration of GBM cells, and the difference was statistically significant (P<0.05). Knockdown of ZDHHC12 also caused changes in EMT-related markers. Restoration of YAP1 reversed the changes in GBM tumor properties induced by the knockdown of ZDHHC12. In the TCGA database, the expression of ZDHHC12 was also closely related to the prognosis of GBM patients. The expression of ZDHHC12 in tissues was positively correlated with YAP1 expression. Conclusion: ZDHHC12 is highly expressed in GBM and positively related to YAP1, and the ZDHHC12/YAP1 axis regulates GBM tumor characteristics.

Key words: Glioblastoma, Zinc finger DHHC domain-containing protein 12, Yes-associated protein 1, Epithelial-mesenchymal transition

CLC Number:

R739.4

ZHANG Qixiang, YOU Yongping. ZDHHC12 regulates tumor properties through YAP1 in glioblastoma[J]. China Oncology, 2022, 32(6): 527-534.

Figures/Tables 4

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