nach oben

Erschienen in:

01.03.2024 | Research

CPLX2 is a novel tumor suppressor and improves the prognosis in glioma

verfasst von: Yuanbing Chen, Jieling Ning, Long Shu, Lingzhi Wen, Bokang Yan, Zuli Wang, Junhong Hu, Xiaokun Zhou, Yongguang Tao, Xuewei Xia, Jun Huang

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2024

Einloggen, um Zugang zu erhalten

Abstract

Background

Glioma is a type of malignant cancer that affect the central nervous system. New predictive biomarkers have been investigated in recent years, but the clinical prognosis for glioma remains poor. The function of CPLX2 in glioma and the probable molecular mechanism of tumor suppression were the focus of this investigation.

Methods

The glioma transcriptome profile was downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases for analysis of CPLX2 expression in glioma. RT-qPCR was performed to detect the expression of CPLX2 in 68 glioma subjects who have been followed up. Kaplan-Meier survival analyses were conducted to assess the effect of CPLX2 on the prognosis of glioma patients. The knockdown and overexpressed cell lines of CPLX2 were constructed to investigate the impact of CPLX2 on glioma. The cell growth, colony formation, and tumor formation in xenograft were performed.

Results

The expression of CPLX2 was downregulated in glioma and was negatively correlated with the grade of glioma. The higher expression of CPLX2 predicted a longer survival, as indicated by the analysis of Kaplan-Meier survival curves. Overexpressed CPLX2 impaired tumorigenesis in glioma progression both in vivo and in vitro. Knocking down CPLX2 promoted the proliferation of glioma cells. The analysis of GSEA and co-expression analysis revealed that CPLX2 may affect the malignancy of glioma by regulating the hypoxia and inflammation pathways.

Conclusions

Our data indicated that CPLX2 functions as a tumor suppressor and could be used as a potential prognostic marker in glioma.

Nur mit Berechtigung zugänglich

Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M (2006) Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol 2(9):494–503 quiz 491 p following 516CrossRefPubMed

De Vleeschouwer S, Bergers G (2017) : Glioblastoma: To Target the Tumor Cell or the Microenvironment? In: Glioblastoma Edited by De Vleeschouwer S. Brisbane (AU): Codon Publications Copyright: The Authors.;

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131(6):803–820CrossRefPubMed

Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS (2019) CBTRUS Statistical Report: primary brain and other Central Nervous System tumors diagnosed in the United States in 2012–2016. Neuro Oncol 21(Suppl 5):v1–v100CrossRefPubMedPubMedCentral

Sant M, Minicozzi P, Lagorio S, Børge Johannesen T, Marcos-Gragera R, Francisci S (2012) Survival of European patients with central nervous system tumors. Int J Cancer 131(1):173–185CrossRefPubMed

Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS, Khasraw M (2020) Management of glioblastoma: state of the art and future directions. Cancer J Clin 70(4):299–312CrossRef

Melia TJ Jr. (2007) Putting the clamps on membrane fusion: how complexin sets the stage for calcium-mediated exocytosis. FEBS Lett 581(11):2131–2139CrossRefPubMed

Tang J, Maximov A, Shin OH, Dai H, Rizo J, Südhof TC (2006) A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell 126(6):1175–1187CrossRefPubMed

Komatsu H, Kakehashi A, Nishiyama N, Izumi N, Mizuguchi S, Yamano S, Inoue H, Hanada S, Chung K, Wei M et al (2013) Complexin-2 (CPLX2) as a potential prognostic biomarker in human lung high grade neuroendocrine tumors. Cancer Biomark 13(3):171–180CrossRefPubMed

10.

Gu W, Ren JH, Zheng X, Hu XY, Hu MJ (2019) Comprehensive analysis of expression profiles of long non–coding RNAs with associated ceRNA network involved in gastric cancer progression. Mol Med Rep 20(3):2209–2218PubMedPubMedCentral

11.

Wei B, Wang R, Wang L, Du C (2020) Prognostic factor identification by analysis of the gene expression and DNA methylation data in glioma. Math Biosci Engineering: MBE 17(4):3909–3924CrossRef

12.

Hass J, Walton E, Kirsten H, Turner J, Wolthusen R, Roessner V, Sponheim SR, Holt D, Gollub R, Calhoun VD et al (2015) Complexin2 modulates working memory-related neural activity in patients with schizophrenia. Eur Arch Psychiatry Clin NeuroSci 265(2):137–145CrossRefPubMed

13.

Radyushkin K, El-Kordi A, Boretius S, Castaneda S, Ronnenberg A, Reim K, Bickeböller H, Frahm J, Brose N, Ehrenreich H (2010) Complexin2 null mutation requires a ‘second hit’ for induction of phenotypic changes relevant to schizophrenia. Genes Brain Behav 9(6):592–602CrossRefPubMed

14.

Gibson HE, Reim K, Brose N, Morton AJ, Jones S (2005) A similar impairment in CA3 mossy fibre LTP in the R6/2 mouse model of Huntington’s Disease and in the complexin II knockout mouse. Eur J Neurosci 22(7):1701–1712CrossRefPubMed

15.

Chung YS, Choo BKM, Ahmed PK, Othman I, Shaikh MF (2020) : Orthosiphon Stamineus proteins Alleviate Pentylenetetrazol-Induced seizures in zebrafish. Biomedicines 8(7)

16.

Shi Y, Tao Y, Jiang Y, Xu Y, Yan B, Chen X, Xiao L, Cao Y (2012) Nuclear epidermal growth factor receptor interacts with transcriptional intermediary factor 2 to activate cyclin D1 gene expression triggered by the oncoprotein latent membrane protein 1. Carcinogenesis 33(8):1468–1478CrossRefPubMed

17.

Jiang Y, Yan B, Lai W, Shi Y, Xiao D, Jia J, Liu S, Li H, Lu J, Li Z et al (2015) Repression of hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8. Oncogene 34(50):6079–6091CrossRefPubMedPubMedCentral

18.

Mao C, Wang X, Liu Y, Wang M, Yan B, Jiang Y, Shi Y, Shen Y, Liu X, Lai W et al (2018) A G3BP1-Interacting lncRNA promotes ferroptosis and apoptosis in Cancer via Nuclear sequestration of p53. Cancer Res 78(13):3484–3496CrossRefPubMedPubMedCentral

19.

Yan B, Liu S, Shi Y, Liu N, Chen L, Wang X, Xiao D, Liu X, Mao C, Jiang Y et al (2018) Activation of AhR with nuclear IKKα regulates cancer stem-like properties in the occurrence of radioresistance. Cell Death Dis 9(5):490CrossRefPubMedPubMedCentral

20.

Makuuchi R, Terashima M, Kusuhara M, Nakajima T, Serizawa M, Hatakeyama K, Ohshima K, Urakami K, Yamaguchi K (2017) Comprehensive analysis of gene mutation and expression profiles in neuroendocrine carcinomas of the stomach. Biomed Res (Tokyo Japan) 38(1):19–27CrossRef

21.

Dono A, Ballester LY, Primdahl D, Esquenazi Y, Bhatia A (2021) IDH-Mutant Low-grade glioma: advances in molecular diagnosis, management, and future directions. Curr Oncol Rep 23(2):20CrossRefPubMed

22.

Chen R, Smith-Cohn M, Cohen AL, Colman H (2017) Glioma subclassifications and their clinical significance. Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics 14(2):284–297CrossRefPubMed

23.

Glynn D, Gibson HE, Harte MK, Reim K, Jones S, Reynolds GP, Morton AJ (2010) Clorgyline-mediated reversal of neurological deficits in a complexin 2 knockout mouse. Hum Mol Genet 19(17):3402–3412CrossRefPubMed

24.

Tsuru E, Oryu K, Sawada K, Nishihara M, Tsuda M (2019) Complexin 2 regulates secretion of immunoglobulin in antibody-secreting cells. Immun Inflamm Dis 7(4):318–325CrossRefPubMedPubMedCentral

25.

Pan H, Oliveira B, Saher G, Dere E, Tapken D, Mitjans M, Seidel J, Wesolowski J, Wakhloo D, Klein-Schmidt C et al (2019) Uncoupling the widespread occurrence of anti-NMDAR1 autoantibodies from neuropsychiatric Disease in a novel autoimmune model. Mol Psychiatry 24(10):1489–1501CrossRefPubMed

26.

Eissa N, Hussein H, Hendy GN, Bernstein CN, Ghia JE (2018) Chromogranin-A and its derived peptides and their pharmacological effects during intestinal inflammation. Biochem Pharmacol 152:315–326CrossRefPubMed

27.

Mahata SK, Corti A (2019) Chromogranin A and its fragments in cardiovascular, immunometabolic, and cancer regulation. Ann N Y Acad Sci 1455(1):34–58CrossRefPubMedPubMedCentral

28.

Chen X, Zhao MZ, Miao BP, Liu ZQ, Yang G, Liu JQ, Yang PC, Song JP (2020) Inhibition of Bcl2L12 attenuates Eosinophilia-related inflammation in the heart. Front Immunol 11:1955CrossRefPubMedPubMedCentral

29.

Varghese JF, Patel R, Yadav UCS (2019) Sterol regulatory element binding protein (SREBP) -1 mediates oxidized low-density lipoprotein (oxLDL) induced macrophage foam cell formation through NLRP3 inflammasome activation. Cell Signal 53:316–326CrossRefPubMed

30.

Uğurel E, Şehitoğlu E, Tüzün E, Kürtüncü M, Çoban A, Vural B (2016) Increased complexin-1 and decreased miR-185 expression levels in Behçet’s Disease with and without neurological involvement. Neurol Sciences: Official J Italian Neurol Soc Italian Soc Clin Neurophysiol 37(3):411–416CrossRef

31.

Frontinan-Rubio J, Llanos-Gonzalez E, Garcia-Carpintero S, Peinado JR, Ballesteros-Yanez I, Rayo MV, de la Fuente J, Perez-Garcia VM, Perez-Romasanta LA, Malumbres M et al (2023) CoQ(10) reduces glioblastoma growth and infiltration through proteome remodeling and inhibition of angiogenesis and inflammation. Cell Oncol (Dordr) 46(1):65–77CrossRefPubMed

32.

Zhu C, Kros JM, Cheng C, Mustafa D (2017) The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies. Neuro Oncol 19(11):1435–1446CrossRefPubMedPubMedCentral

33.

Durrani IA, Bhatti A, John P (2021) The prognostic outcome of ‘type 2 Diabetes Mellitus and Breast cancer’ association pivots on hypoxia-hyperglycemia axis. Cancer Cell Int 21(1):351CrossRefPubMedPubMedCentral

34.

Wei B, Li L, He A, Zhang Y, Sun M, Xu Z (2016) Hippocampal NMDAR-Wnt-catenin signaling disrupted with cognitive deficits in adolescent offspring exposed to prenatal hypoxia. Brain Res 1631:157–164CrossRefPubMed

35.

Biswal S, Das D, Barhwal K, Kumar A, Nag TC, Thakur MK, Hota SK, Kumar B (2017) Epigenetic regulation of SNAP25 prevents Progressive Glutamate Excitotoxicty in hypoxic CA3 neurons. Mol Neurobiol 54(8):6133–6147CrossRefPubMed

36.

Kiouptsi K, Finger S, Garlapati VS, Knorr M, Brandt M, Walter U, Wenzel P, Reinhardt C (2019) : Hypoxia evokes increased PDI and PDIA6 expression in the infarcted myocardium of ex-germ-free and conventionally raised mice. Biology open 8(1)

37.

Malfettone A, Silvestris N, Paradiso A, Mattioli E, Simone G, Mangia A (2012) Overexpression of nuclear NHERF1 in advanced Colorectal cancer: association with hypoxic microenvironment and Tumor invasive phenotype. Exp Mol Pathol 92(3):296–303CrossRefPubMed

38.

Chen Y, Tang M, Xiong J, Gao Q, Cao W, Huang J (2022) GRB10 is a novel oncogene associated with cell proliferation and prognosis in glioma. Cancer Cell Int 22(1):223CrossRefPubMedPubMedCentral

39.

Wu K, Mao YY, Chen Q, Zhang B, Zhang S, Wu HJ, Li Y (2021) Hypoxia-induced ROS promotes mitochondrial fission and cisplatin chemosensitivity via HIF-1alpha/Mff regulation in head and neck squamous cell carcinoma. Cell Oncol (Dordr) 44(5):1167–1181CrossRefPubMed

40.

Mu H, Yu G, Li H, Wang M, Cui Y, Zhang T, Song T, Liu C (2021) Mild chronic hypoxia-induced HIF-2alpha interacts with c-MYC through competition with HIF-1alpha to induce hepatocellular carcinoma cell proliferation. Cell Oncol (Dordr) 44(5):1151–1166CrossRefPubMed

41.

Eltzschig HK, Carmeliet P (2011) Hypoxia and inflammation. N Engl J Med 364(7):656–665CrossRefPubMedPubMedCentral

42.

Masuda S, Kato K, Ishibashi M, Nishibata Y, Sugimoto A, Nakazawa D, Tanaka S, Tomaru U, Tsujino I, Ishizu A (2022) Phorbol 12-myristate 13-acetate stimulation under hypoxia induces nuclear swelling with DNA outflow but not extracellular trap formation of neutrophils. Exp Mol Pathol 125:104754CrossRefPubMed

Titel: CPLX2 is a novel tumor suppressor and improves the prognosis in glioma
verfasst von: Yuanbing Chen
Jieling Ning
Long Shu
Lingzhi Wen
Bokang Yan
Zuli Wang
Junhong Hu
Xiaokun Zhou
Yongguang Tao
Xuewei Xia
Jun Huang
Publikationsdatum: 01.03.2024
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2024
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-023-04548-4

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Demenz Nachrichten

Der Einsatz von Antipsychotika gegen psychische und Verhaltenssymptome in Zusammenhang mit Demenzerkrankungen erfordert eine sorgfältige Nutzen-Risiken-Abwägung. Neuen Erkenntnissen zufolge sind auf der Risikoseite weitere schwerwiegende Ereignisse zu berücksichtigen.

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2024

Stereotactic radiosurgery and bevacizumab for recurrent glioblastoma

Correction to: The effectiveness and safety of proton beam radiation therapy in children and young adults with Central Nervous System (CNS) tumours: a systematic review

Predictive role of intracranial PD-L1 expression in a real-world cohort of NSCLC patients treated with immune checkpoint inhibition following brain metastasis resection

Imaging predictors of 4q12 amplified and RB1 mutated glioblastoma IDH-wildtype

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review