Background:　New　targeted　drugs　about　angiogenesis　could　develop　the　treatment　of　glioma.　We　aimed　to　explore　the　role　of　phosducin　like　3　(PDCL3)　in　angiogenesis　of　glioma.　Materials　and　Methods:　RNA　sequencing　data　and　matched　clinical　data　were　downloaded　from　The　Cancer　Genome　Atlas　(TCGA)　and　Chinese　Glioma　Genome　Atlas　(CGGA)　databases.　To　screen　for　the　reliable　genes　with　the　filtering　analyses,　survival,　multivariate　Cox,　receiver　operating　characteristic　(ROC)　curve　filtration,　and　clinical　correlation　analyses　were　performed.　The　PDCL3　gene　was　validated　by　immunohistochemistry　as　a　reliable　gene　for　further　analysis.　Then　we　used　the　combined　data　of　TCGA　and　Genotype-Tissue　Expression　from　UCSC　to　detect　the　differential　gene　expression　of　PDCL3.　Related　signal　pathways　in　glioma　were　explored　by　the　gene　set　enrichment　analysis　and　co-expression　analysis.　Lastly,　we　performed　in　vitro　experiments　to　verify　the　gene　functions　and　related　mechanisms.　Results:　The　three　filtering　analyses　and　immunostaining　indicated　that　the　expression　of　PDCL3　in　glioma　tissues　was　higher　than　the　normal　tissues.　Gene　function　analysis　showed　that　PDCL3　activated　the　vascular　endothelial　growth　factor　(VEGF)　signal　pathway,　and　its　mechanism　was　related　to　pathways　in　cancer,　like　NOD　like　receptor　signaling　pathway,　the　RIG-I　like　receptor　signaling　pathway　and　the　P53　signaling　pathway　by　MAPK/AKT　in　gliomas.　This　suggested　that　the　proliferation,　migration　and　invasion　of　glioma　cells　might　be　inhibited　by　the　downregulation　of　PDCL3　in　vitro,　which　may　be　related　to　the　activation　of　VEGF　signaling　pathway.　Conclusion:　We　demonstrated　that　PDCL3　could　function　as　an　independent　adverse　prognostic　marker　in　glioma.　Its　pro-oncogenic　mechanism　may　be　related　to　the　VEGF　signaling　pathway.　©　2024　John　Wiley　&　Sons　Ltd.