ZBTB20 Suppresses Tumor Growth in Glioblastoma Through Activating the TET1/FAS/caspase‑3 Pathway

Overview

Journal Oncol Lett

Specialty Oncology

Date 2024 Jun 17

PMID 38881713

Authors

Ping Duan

Bo Li

Yifan Zhou

Huanhuan Cao

Shiyue Chen

Ying Xing

Affiliations

Soon will be listed here.

Abstract

Zinc finger and BTB domain containing 20 (ZBTB20) is a key transcription repressor that regulates multiple physiological and pathophysiological processes. Thus far, the role of ZBTB20 in glioblastoma (GBM), a World Health Organization grade IV glioma, remains unclear. In the present study, the expression profile data of ZBTB20 in GBM tissues from public databases was analyzed. It was found that ZBTB20 expression in GBM tissues was significantly lower than that measured in lower grade glioma tissues. Furthermore, patients with GBM with lower ZBTB20 expression were associated with a shorter overall survival time. Gain- and loss-of-function experiments in GBM cells were also performed. The results demonstrated that ZBTB20 overexpression decreased GBM cell proliferation, while ZBTB20 knockdown significantly enhanced it. Cell cycle analysis showed the ZBTB20 overexpression may have inhibited proliferation through cell cycle arrest at the G2/M phase, while ZBTB20 knockdown increased the percentages of cells in both the S phase and G2/M phase. Ten-eleven translocation 1 (TET1) is an important tumor suppressor involved in the formation of various types of tumor, and it was upregulated in ZBTB20-overexpressing GBM cells. It was further demonstrated that ZBTB20 activated the TET1/FAS/caspase-3 pathway. The results of the present study therefore indicated the potential role of ZBTB20 as a tumor suppressor and therapeutic target for GBM.

References

Wang J, Chun H, Wong W, Spencer D, Lenardo M . Caspase-10 is an initiator caspase in death receptor signaling. Proc Natl Acad Sci U S A. 2001; 98(24):13884-8. PMC: 61136. DOI: 10.1073/pnas.241358198. View

Liu J, Jiang J, Hui X, Wang W, Fang D, Ding L . Mir-758-5p Suppresses Glioblastoma Proliferation, Migration and Invasion by Targeting ZBTB20. Cell Physiol Biochem. 2018; 48(5):2074-2083. DOI: 10.1159/000492545. View

de la Rosa J, Weber J, Friedrich M, Li Y, Rad L, Ponstingl H . A single-copy Sleeping Beauty transposon mutagenesis screen identifies new PTEN-cooperating tumor suppressor genes. Nat Genet. 2017; 49(5):730-741. PMC: 5409503. DOI: 10.1038/ng.3817. View

Kan H, Huang Y, Li X, Liu D, Chen J, Shu M . Zinc finger protein ZBTB20 is an independent prognostic marker and promotes tumor growth of human hepatocellular carcinoma by repressing FoxO1. Oncotarget. 2016; 7(12):14336-49. PMC: 4924719. DOI: 10.18632/oncotarget.7425. View

Johnson K, Houseman E, King J, Von Herrmann K, Fadul C, Christensen B . 5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients. Nat Commun. 2016; 7:13177. PMC: 5133638. DOI: 10.1038/ncomms13177. View

Zhang Y, Zhou X, Zhang M, Cheng L, Zhang Y, Wang X . ZBTB20 promotes cell migration and invasion of gastric cancer by inhibiting IκBα to induce NF-κB activation. Artif Cells Nanomed Biotechnol. 2019; 47(1):3862-3872. DOI: 10.1080/21691401.2019.1670188. View

Neumann L, Pforr C, Beaudouin J, Pappa A, Fricker N, Krammer P . Dynamics within the CD95 death-inducing signaling complex decide life and death of cells. Mol Syst Biol. 2010; 6:352. PMC: 2858442. DOI: 10.1038/msb.2010.6. View

Zhao J, Ren K, Tang J . Zinc finger protein ZBTB20 promotes cell proliferation in non-small cell lung cancer through repression of FoxO1. FEBS Lett. 2014; 588(24):4536-42. DOI: 10.1016/j.febslet.2014.10.005. View

Wu B, Brenner C . Suppression of TET1-dependent DNA demethylation is essential for KRAS-mediated transformation. Cell Rep. 2014; 9(5):1827-1840. PMC: 4268240. DOI: 10.1016/j.celrep.2014.10.063. View

10.

Yang F, Xu M, Wang S, Song L, Yu D, Li Y . Gain-Of-Function E76K-Mutant SHP2 Promotes Cell Proliferation, Metastasis, And Tumor Growth In Glioblastoma Through Activation Of The ERK/CREB Pathway. Onco Targets Ther. 2019; 12:9435-9447. PMC: 6844267. DOI: 10.2147/OTT.S222881. View

11.

Sun Y, Liu W, Liu T, Feng X, Yang N, Zhou H . Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res. 2015; 35(6):600-4. DOI: 10.3109/10799893.2015.1030412. View

12.

Ostrom Q, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C . CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012. Neuro Oncol. 2015; 17 Suppl 4:iv1-iv62. PMC: 4623240. DOI: 10.1093/neuonc/nov189. View

13.

Gong R, Li H, Liu Y, Wang Y, Ge L, Shi L . Gab2 promotes acute myeloid leukemia growth and migration through the SHP2-Erk-CREB signaling pathway. J Leukoc Biol. 2022; 112(4):669-677. DOI: 10.1002/JLB.2A0421-221R. View

14.

Lo H . Targeting Ras-RAF-ERK and its interactive pathways as a novel therapy for malignant gliomas. Curr Cancer Drug Targets. 2010; 10(8):840-8. PMC: 3615246. DOI: 10.2174/156800910793357970. View

15.

Pirnia F, Schneider E, Betticher D, Borner M . Mitomycin C induces apoptosis and caspase-8 and -9 processing through a caspase-3 and Fas-independent pathway. Cell Death Differ. 2002; 9(9):905-14. DOI: 10.1038/sj.cdd.4401062. View

16.

Nielsen J, Blom J, Noraberg J, Jensen N . Zbtb20-induced CA1 pyramidal neuron development and area enlargement in the cerebral midline cortex of mice. Cereb Cortex. 2009; 20(8):1904-14. DOI: 10.1093/cercor/bhp261. View

17.

Zhang W, Mi J, Li N, Sui L, Wan T, Zhang J . Identification and characterization of DPZF, a novel human BTB/POZ zinc finger protein sharing homology to BCL-6. Biochem Biophys Res Commun. 2001; 282(4):1067-73. DOI: 10.1006/bbrc.2001.4689. View

18.

Ji J, You Q, Zhang J, Wang Y, Cheng J, Huang X . Downregulation of TET1 Promotes Glioma Cell Proliferation and Invasion by Targeting Wnt/-Catenin Pathway. Anal Cell Pathol (Amst). 2021; 2021:8980711. PMC: 8677395. DOI: 10.1155/2021/8980711. View

19.

Suita H, Shinomiya T, Nagahara Y . Caspase-6 Induces 7A6 Antigen Localization to Mitochondria During FAS-induced Apoptosis of Jurkat Cells. Anticancer Res. 2017; 37(4):1697-1704. DOI: 10.21873/anticanres.11501. View

20.

Rokhlin O, Glover R, Cohen M . Fas-mediated apoptosis in human prostatic carcinoma cell lines occurs via activation of caspase-8 and caspase-7. Cancer Res. 1998; 58(24):5870-5. View