ZDHHC15 promotes glioma malignancy and acts as a novel prognostic biomarker for patients with glioma

胶质瘤 基因敲除 癌症研究 生物 细胞周期 小桶 恶性肿瘤 外科肿瘤学 信号转导 肿瘤进展 医学 细胞 肿瘤科 基因表达 癌症 细胞培养 基因 转录组 细胞生物学 遗传学
作者
Zhen‐Yuan Liu,Tian Lan,Feng Tang,Yong-Ze He,Jinsheng Liu,Jin‐Zhou Yang,Xi Chen,Xinghuan Wang,Zhi-Qiang Li
出处
期刊:BMC Cancer [Springer Nature]
卷期号:23 (1) 被引量:10
标识
DOI:10.1186/s12885-023-10883-6
摘要

Abstract Background Glioma is the most common and aggressive tumor in the adult brain. Recent studies have indicated that Zinc finger DHHC-type palmitoyltransferases (ZDHHCs) play vital roles in regulating the progression of glioma. ZDHHC15, a member of the ZDHHCs family, participates in various physiological activities in the brain. However, the biological functions and related mechanisms of ZDHHC15 in glioma remain poorly understood. Methods Data from multiple glioma-associated datasets were used to investigate the expression profiles and potential biological functions of ZDHHC15 in glioma. Expression of ZDHHC15 and its association with clinicopathological characteristics in glioma were validated by quantitative reverse transcription PCR (RT-qPCR) and immunohistochemical experiments. GO enrichment analysis, KEGG analysis, GSEA analysis, CCK-8, EdU, transwell, and western blotting assays were performed to confirm the functions and mechanism of ZDHHC15 in glioma. Moreover, we performed Kaplan-Meier analysis and Cox progression analysis to explore the prognostic significance of ZDHHC15 in glioma patients. Results ZDHHC15 expression was significantly up-regulated in glioma and positively associated with malignant phenotypes. Results from the GO and KEGG enrichment analysis revealed that ZDHHC15 was involved in regulating cell cycle and migration. Knockdown of ZDHHC15 inhibited glioma cell proliferation and migration, while overexpression of ZDHHC15 presented opposite effects on glioma cells. Besides, results from GSEA analysis suggested that ZDHHC15 was enriched in STAT3 signaling pathway. Knockdown or overexpression of ZDHHC15 indeed affected the activation of STAT3 signaling pathway. Additionally, we identified ZDHHC15 as an independent prognostic biomarker in glioma, and higher expression of ZDHHC15 predicted a poorer prognosis in glioma patients. Conclusion Our findings suggest that ZDHHC15 promotes glioma malignancy and can serve as a novel prognostic biomarker for glioma patients. Targeting ZDHHC15 may be a promising therapeutic strategy for glioma.
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