Involvement of ZDHHC9 in lung adenocarcinoma: regulation of PD-L1 stability via palmitoylation.

Zhe Li, Da Jiang, Fengling Liu, Ying Li

In vitro cellular & developmental biology. Animal 2023 Mar

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Palmitoylation is a post-translational modification occurring on cysteine residues, which process is catalyzed by a family of zinc finger Asp-His-His-Cys (DHHC) domain-containing (ZDHHC) protein acyltransferases. As a family member, ZDHHC9 plays a crucial role in varied malignancies by regulating protein stability via protein substrate palmitoylation. Based on the bioinformatic analysis of GEO gene microarray GSE75037 (|log2 fold change|> 1, P < 0.05), ZDHHC9 was defined as a significantly upregulated gene in lung adenocarcinoma (LUAD), which was also confirmed in our collected clinical specimens. It is necessary to explore the biological function of ZDHHC9 in LUAD cells. The follow-up functional experiments revealed that ZDHHC9 deficiency inhibited proliferation, migration, and invasion, while stimulated apoptosis in HCC827 cells. Besides, these malignant phenotypes could be accelerated by ZDHHC9 overexpression in A549. Moreover, we revealed that ZDHHC9 knockdown could promote PD-L1 protein degradation by reducing its palmitoylation level. The reduction of PD-L1 protein level could enhance anti-tumor immunity and inhibit the growth of LUAD cells. Therefore, our study uncovers the tumor-promoting role of ZDHHC9 in LUAD via regulating PD-L1 stability through palmitoylation, highlighting ZDHHC9 as a novel therapeutic target for LUAD. © 2023. The Society for In Vitro Biology.

Citation

Zhe Li, Da Jiang, Fengling Liu, Ying Li. Involvement of ZDHHC9 in lung adenocarcinoma: regulation of PD-L1 stability via palmitoylation. In vitro cellular & developmental biology. Animal. 2023 Mar;59(3):193-203