High immune-cell infiltration in
glioblastomas (GBMs) leads to
immunotherapy resistance. Emerging evidence has shown that zinc finger Asp-
His-His-Cyc-type (ZDHHC) palmitoyl
transferases participate in regulating
tumor progression and the immune microenvironment. In the present study, a large cohort of patients with
gliomas from The
Cancer Genome Atlas (TCGA) and Rembrandt databases was included to perform omics analysis of ZDHHCs in
gliomas.
CCK-8, flow cytometry, quantitative real-time PCR, western blotting, and transwell assays were performed to determine the effects of ZDHHC inhibition on
glioma cells and microglia. We found that five (ZDHHC11, ZDHHC12, ZDHHC15, ZDHHC22, and ZDHHC23) out of 23 ZDHHCs were aberrantly expressed in
gliomas and might play their roles through the
phosphatidylinositol 3-kinase/
protein kinase B (PI3K/AKT) signaling pathway. Further results indicated that inhibition of ZDHHCs with
2-bromopalmitate (2-BP) suppressed
glioma-cell viability and autophagy, as well as promoted apoptosis. Targeting ZDHHCs also promoted the sensitivity of
glioma cells to
temozolomide (TMZ)
chemotherapy. In addition, the inhibition of ZDHHCs weakened the migratory ability of microglia induced by
glioma cells in vitro and in vivo. Taken together, our findings suggest that the inhibition of ZDHHCs suppresses
glioma-cell viability and microglial infiltration. Targeting ZDHHCs may be promising for
glioma treatments.