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

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.

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

“…Recent studies have confirmed a clear link between high zDHHC15 expression and the malignant glioma phenotype, and zDHHC15 plays a key role in promoting the proliferation and migration of glioma cells by activating the STAT3 signaling pathway. Researchers have also suggested that zDHHC15 may be a new prognostic biomarker for patients with glioma and that targeting zDHHC15 could provide a promising strategy for the treatment of glioma ( Liu et al, 2023 ). Local anesthetics may attenuate zDHHC15 transcription, reduce GP130 palmitoylation levels and membrane localization, and thus inhibit IL-6/STAT3 signaling activation.…”

Inhibition of ZDHHC16 promoted osteogenic differentiation and reduced ferroptosis of dental pulp stem cells by CREB

“…Recent research has underscored the extensive participation of ZDHHCs in the progression of various diseases. Enhancing glioma malignancy, ZDHHC15 emerged as a potential novel prognostic biomarker for glioma patients [ 25 ]. Palmitoylation played a crucial role in enhancing osteoclast differentiation and activity, presenting itself as a plausible therapeutic target for addressing osteoporosis and other diseases associated with osteoclast dysfunction [ 26 ].…”

Diverse Roles of Protein Palmitoylation in Cancer Progression, Immunity, Stemness, and Beyond

“…For example, an RNAi-based screen targeting, all 23 members of the ZDHHC family in non-small lung cancer (NSCLC) identified ZDHHC5 to be essential for the growth of NSCLC but not normal human bronchial epithelial cells [ 54 ]. In gliomas, inactivation of ZDHHC15 blocked glioma cells proliferation by decreasing activation of Signal Transducer and Activator of Transcription 3 (STAT3) [ 55 ] and knockdown of ZDHHC12 reduced the growth, migration, and invasion capabilities of glioma cells [ 56 , 57 ]. In pancreatic cancer, knockdown of ZDHHC3 impaired tumor progression in a xenograft mice model [ 58 ], whereas inactivation of ZDHHC9 modified the tumor microenvironment from an immunosuppressive to a proinflammatory environment and, thus, suppressed tumor growth [ 59 ].…”