|Table of Contents|

The expression of SGPL1 in glioma tissue and its effect on the proliferation and apoptosis of glioma cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 08
Page:
1420-1427
Research Field:
Publishing date:

Info

Title:
The expression of SGPL1 in glioma tissue and its effect on the proliferation and apoptosis of glioma cells
Author(s):
ZENG Jianling1; LIU Zhaohui1; 2; TAN Fenghua1; 3; DUAN Lili1; 3; LI Jia1; 3; HU Zheng1; 3
1.Translational Medicine Institute,the First People's Hospital of Chenzhou,Hengyang Medical School,University of South China,Hunan Chenzhou 423000,China;2.Department of Respiratory and Critical Care Medicine,the First People's Hospital of Chenzhou,Hunan Chenzhou 423000,China;3.the First Clinical College of Xiangnan University,the First People's Hospital of Chenzhou Affiliated to Xiangnan University,Hunan Chenzhou 423000,China.
Keywords:
glioma; SGPL1; proliferation; apoptosis
PACS:
R739.41
DOI:
10.3969/j.issn.1672-4992.2023.08.007
Abstract:
Objective:To investigate the expression of SGPL1 in glioma tissue and the effect of SGPL1 expression on the proliferation and apoptosis of glioma cells.Methods:The differential expression of SGPL1 in glioma clinical tumor tissue and normal nerve tissue was analyzed by the TCGA and PROGgene online database,and the relationship between its expression and prognostic survival in glioma patients was analyzed.Knockdown and overexpression of SGPL1 were performed in the glioma cell lines U251 and U87,respectively.The mRNA and protein expression levels of SGPL1 were determined by the RT-qPCR and Western blot.After SGPL1 knockdown and overexpression,cell proliferation was detected by CCK-8 assay and cell cloning assay.The apoptosis was analyzed by flow cytometry and caspase3/7 enzyme activity reagent.The expressions of caspase3,PARP and CyclinD1 were detected by Western blot.The content of S1P in the cells was detected by ELISA.RT-qPCR was used to detect the expression of S1PR5.RNA-seq was used to analyze the signaling pathway regulated by SGPL1 in glioma cells.Western blot assay was used to detect Phospho-p38-MAPK,Phospho-ERK,Phospho-STAT3,and Phospho-NF-κB(p65) expression after SGPL1 knockdown and overexpression.Results:TCGA and PROGgene online database analysis showed that SGPL1 was highly expressed in glioma tissues and negatively correlated with the prognostic survival of glioma patients.After SGPL1 knockdown in U251 cells,cell proliferation was inhibited and apoptosis was increased.Overexpression of SGPL1 in U87 cells significantly promoted cell proliferation.The expression of SGPL1 had no significant effect on S1P signaling pathway.RNA-seq results showed that SGPL1 regulated the cell proliferation and death signaling pathway in glioma cells.Knockdown and overexpression of SGPL1 affected the proliferation and growth signaling pathways of p38-MAPK,ERK,STAT3 and NF-κB(p65).Conclusion:SGPL1 is highly expressed in gliomas tissue and negatively correlated with survival prognosis.SGPL1 regulates the cell proliferation and growth signaling pathways of p38-MAPK,ERK,STAT3 and NF-κB(p65) in glioma cells,and its expression can affect the proliferation and apoptosis of glioma cells,which may be a potential tumor marker and therapeutic molecular target.

References:

[1] OSTROM QT,GITTLEMAN H,LIAO P,et al.CBTRUS Statistical Report:Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014［J］.Neuro Oncol,2017,19(suppl_5):v1-v88.
[2] HAMADA T,AKAHANE T,YOKOYAMA S,et al.An oncogenic splice variant of PDGFRalpha in adult glioblastoma as a therapeutic target for selective CDK4/6 inhibitors［J］.Sci Rep,2022,12 (1):1275.
[3] LAPOINTE S,PERRY A,BUTOWSKI NA.Primary brain tumours in adults［J］.Lancet,2018,392(10145):432-446.
[4] GAULT CR,OBEID LM,HANNUN YA.An overview of sphingolipid metabolism:from synthesis to breakdown［J］.Adv Exp Med Biol,2010,688:1-23.
[5] MAHARAJ A,WILLIAMS J,BRADSHAW T,et al.Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction［J］.J Steroid Biochem Mol Biol,2020,202:105730.
[6] MACEYKA M,HARIKUMAR KB,MILSTIEN S,et al.Sphingosine-1-phosphate signaling and its role in disease［J］.Trends Cell Biol,2012,22(1):50-60.
[7]GENNERO I,FAUVEL J,NIETO M,et al.Apoptotic effect of sphingosine 1-phosphate and increased sphingosine 1-phosphate hydrolysis on mesangial cells cultured at low cell density［J］.J Biol Chem,2002,277(15):12724-12734.
[8]BRIZUELA L,ADER I,MAZEROLLES C,et al.First evidence of sphingosine 1-phosphate lyase protein expression and activity downregulation in human neoplasm:implication for resistance to therapeutics in prostate cancer［J］.Mol Cancer Ther,2012,11(9):1841-1851.
[9] COLI S,VAN VELDHOVEN PP,KEDJOUAR B,et al.Disruption of sphingosine 1-phosphate lyase confers resistance to chemotherapy and promotes oncogenesis through Bcl-2/Bcl-xL upregulation［J］.Cancer Res,2009,69(24):9346-9353.
[10] HIBBS K,SKUBITZ KM,PAMBUCCIAN SE,et al.Differential gene expression in ovarian carcinoma:identification of potential biomarkers［J］.Am J Pathol,2004,165(2):397-414.
[11]OSKOUIAN B,SOORIYAKUMARAN P,BOROWSKY AD,et al.Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer［J］.Proc Natl Acad Sci USA,2006,103(46):17384-17389.
[12] DEGAGN E,PANDURANGAN A,BANDHVULA P,et al.Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs［J］.J Clin Invest,2014,124(12):5368-5384.
[13] BOROWSKY AD,BANDHUVULA P,KUMAR A,et al.Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues［J］.J Lipid Res,2012,53(9):1920-1931.
[14] URANBILEG B,IKEDA H,KURANO M,et al.Increased mRNA levels of sphingosine kinases and S1P lyase and reduced levels of S1P were observed in hepatocellular carcinoma in association with poorer differentiation and earlier recurrence［J］.PLoS One,2016,11(2):e0149462.
[15] VISHWAKARMA S,AGARWAL R,GOEL SK,et al.Altered expression of sphingosine-1-phosphate metabolizing enzymes in oral cancer correlate with clinicopathological attributes［J］.Cancer Invest,2017,35(2):139-141.
[16] 王伟,王茂德,姜海涛,等.基于TCGA与GTEx数据库分析AEBP1基因在不同分型胶质瘤中的表达及对预后的影响［J］.西安交通大学学报(医学版),2022,43(04):503-508. WANG W,WANG MD,JIANG HT,et al.Expression of AEBP1 and its prognostic role in glioma based on the data-mining of TCGA and GTEx databases［J］.Journal of Xi'an Jiaotong University（Medical Sciences）,2022,43(04):503-508.
[17] 李香凝.SGPL1促进肺腺癌增殖和迁移的作用及机制研究［D］.衡阳:南华大学,2021. LI XN.Study on the effect and mechanism of SGPL1 in promoting the proliferation and migration of lung adenocarcinoma［D］.Hengyang:University of South China,2021.
[18] SPIEGEL S,MILSTIEN S.The outs and the ins of sphingosine-1-phosphate in immunity［J］.Nat Rev Immunol,2011,11(6):403-415.
[19] MCGOWAN EM,HADDADI N,NASSIF NT,et al.Targeting the SphK-S1P-SIPR pathway as a potential therapeutic approach for COVID-19［J］.Int J Mol Sci,2020,21(19):7189.
[20] GIUSTO K,ASHBY CR.Investigating the Et-1/SphK/S1P pathway as a novel approach for the prevention of inflammation-induced preterm birth［J］.Curr Pharm Des,2018,24(9):983-988.
[21] SHI ZA,LI TT,KANG DL,et al.Fingolimod attenuates renal ischemia/reperfusion-induced acute lung injury by inhibiting inflammation and apoptosis and modulating S1P metabolism［J］.J Int Med Res,2021,49(8):675873562.
[22] HU SL,HUANG CC,TSENG TT,et al.S1P facilitates IL-1β production in osteoblasts via the JAK and STAT3 signaling pathways［J］.Environ Toxicol,2020,35(9):991-997.
[23] SOARES R,AZEVEDO I.Inhibition of S1P by polyphenols prevents inflammation and angiogenesis:NFkappaB,a downstream effector［J］.Free Radic Biol Med,2007,42(2):311.
[24] GARBERS C,APARICIO-SIEGMUND S,ROSE-JOHN S.The IL-6/gp130/STAT3 signaling axis:recent advances towards specific inhibition［J］.Curr Opin Immunol,2015,34:75-82.
[25] SINGH N,BABY D,RAJGURU JP,et al.Inflammation and cancer［J］.Ann Afr Med,2019,18(3):121-126.
[26] MITCHELL K,TROIKE K,SILVER DJ,et al.The evolution of the cancer stem cell state in glioblastoma:emerging insights into the next generation of functional interactions［J］.Neuro Oncol,2021,23(2):199-213.
[27] LIU T,MA W,XU H,et al.PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma［J］.Nat Commun,2018,9(1):3439.
[28] HAI L,ZHUANG C,LI T,et al.Notch1 is a prognostic factor that is distinctly activated in the classical and proneural subtype of glioblastoma and that promotes glioma cell survival via the NF-κB(p65) pathway［J］.Cell Death Dis,2018,9(2):158.
[29] XU J,ZHANG Z,QIAN M,et al.Cullin-7 (CUL7) is overexpressed in glioma cells and promotes tumorigenesis via NF-κB activation.［J］.Journal of Experimental & Clinical Cancer Research:CR,2020,39(1):59.
[30] NAPETSCHNIG J,WU H.Molecular basis of NF-kappaB signaling［J］.Annu Rev Biophys,2013,42:443-468.
[31] LEE H,DENG J,KUJAWSKI M,et al.STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors［J］.Nat Med,2010,16(12):1421-1428.
[32] JIANG Y,ZHOU J,HOU D,et al.Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF-beta1/Smad signaling pathway［J］.J Pathol,2019,249(1):26-38.
[33] HAN MZ,XU R,XU YY,et al.TAGLN2 is a candidate prognostic biomarker promoting tumorigenesis in human gliomas［J］.J Exp Clin Cancer Res,2017,36(1):155.

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湖南省卫生健康委科研计划项目（编号：202203023459）；郴州市第一人民医院科技创新团队（编号：CX202103）
Last Update: 1900-01-01