The alternatively spliced diacylglycerol kinase gamma-Δexon13 transcript generated under hypoxia promotes glioblastoma progression  

作　　者：MING YANG LIANGZHAO CHU SHUKAI LIN HAN PENG NIYA LONG KAYA XU HUA YANG FENG HAN JIAN LIU 

机构地区：[1]Department of Neurosurgery,The Affiliated Hospital of Guizhou Medical University,Guiyang,550025,China [2]Department of Neurosurgery,Sanya Central Hospital(Hainan Third People’s Hospital),Sanya,572000,China

出　　处：《Oncology Research》2025年第5期1189-1198,共10页肿瘤学研究(英文)

基　　金：funded by Guizhou Province Science and Technology Plan Project Qiankehe Foundation-ZK[2023]General 360,362;Science and Technology Fund project of Guizhou Provincial Health Commission(gzwkj-2022-09,gzwkj-2023-035);National Natural Science Foundation Cultivation Project of Guizhou Medical University(21NSFCP14,gyfynsfc-2022-25);The PhD Scientific Research Launch Fund Project of the Affiliated Hospital of Guizhou Medical University(gyfybsky-2022-02).

摘　　要：Background:Glioblastoma(GBM)is one of the most malignant types of central nervous system tumors.Oxygen deprivation in the tumor microenvironment is thought to be an important factor in promoting GBM progression.However,the mechanisms of hypoxia-promoted tumor progression remain elusive.Methods:Alternative splicing of diacylglycerol kinase gamma(DGKG)-Δexon13 was amplified and verified by PCR-Sanger sequencing.The functions of DGKG and DGKG-Δexon13 were analyzed by Cell counting kit-8(CCK-8),Transwell,Matrigeltranswell experiments,and in vivo orthotropic GBM animal models.Transcriptome analyses were done to find out the regulated genes.Results:In this study,we found that a new transcript DGKG-Δexon13 was generated in GBM under hypoxia via alternative splicing.Moreover,the results of CCK-8,Transwell,and Matrigel-transwell experiments showed that the proliferation,migration,and invasion abilities of U87-MG and T98G were decreased after DGKG knockdown.Compared to wild-type DGKG,DGKG-Δexon13 overexpression significantly promoted cellular proliferation,migration,and invasion abilities in GBM.Furthermore,in vivo,orthotropic GBM animal models analysis showed that the tumor volumes were much smaller in the DGKG knockdown group.However,the tumor sizes in the DGKG and DGKG-Δexon13 rescue groups were restored,especially in the DGKG-Δexon13 group.Transcriptome analysis revealed that MORC1,KLHDC7B,ATP1A2,INHBE,TMEM119,and FGD3 were altered significantly when DGKG was knocked down.IL-16,CCN2,and EFNB3 were specifically regulated by DGKG-Δexon13.Conclusions:Our study found that hypoxia-induced alternative splicing transcript DGKG-Δexon13 promotes GBM proliferation and infiltration,which might provide a new potential target for the clinical treatment and diagnosis of GBM.

关 键 词：Glioblastoma(GBM) HYPOXIA Diacylglycerol kinase gamma(DGKG) Alternative splicing 

分 类 号：R739.41[医药卫生—肿瘤]