YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells

Abstract Background Glioma is a common type of malignant brain tumor with a high mortality and relapse rate. The endosomal sorting complex required for transport (ESCRT) has been reported to be involved in tumorigenesis. However, the molecular mechanisms have not been clarified. Methods Bioinformati...

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Autores principales: Xiaolong Zhu, Hui Yang, Mengying Zhang, Xingwei Wu, Lan Jiang, Xiaocen Liu, Kun Lv
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Lenguaje:EN
Publicado: BMC 2021
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Acceso en línea:https://doaj.org/article/68cd530934ee437c8d8f635e4d8b57f9
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spelling oai:doaj.org-article:68cd530934ee437c8d8f635e4d8b57f92021-12-05T12:23:36ZYTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells10.1186/s12935-021-02304-01475-2867https://doaj.org/article/68cd530934ee437c8d8f635e4d8b57f92021-12-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02304-0https://doaj.org/toc/1475-2867Abstract Background Glioma is a common type of malignant brain tumor with a high mortality and relapse rate. The endosomal sorting complex required for transport (ESCRT) has been reported to be involved in tumorigenesis. However, the molecular mechanisms have not been clarified. Methods Bioinformatics was used to screen the ESCRT subunits highly expressed in glioma tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The function of the ESCRT subunits in glioma cells was examined in vitro. Transcriptome sequencing analyzed the target genes and signaling pathways affected by the ESCRT subunit. Finally, the relationship between m6A (N 6-methyladenosine) modification and high expression of the ESCRT subunit was studied. Results VPS25 was upregulated in glioma tissues, which was correlated with poor prognosis in glioma patients. Furthermore, VPS25 knockdown inhibited the proliferation, blocked the cell cycle, and promoted apoptosis in glioma cells. Meanwhile, VPS25 induced a G0/G1 phase arrest of the cell cycle in glioma cells by directly mediating p21, CDK2, and cyclin E expression, and JAK-signal transducer and activator of transcription (STAT) activation. Finally, YTHDC1 inhibited glioma proliferation by reducing the expression of VPS25. Conclusion These results suggest that VPS25 is a promising prognostic indicator and a potential therapeutic target for glioma.Xiaolong ZhuHui YangMengying ZhangXingwei WuLan JiangXiaocen LiuKun LvBMCarticleYTHDC1VPS25Cell cycleJAK–STATGliomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic YTHDC1
VPS25
Cell cycle
JAK–STAT
Glioma
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
spellingShingle YTHDC1
VPS25
Cell cycle
JAK–STAT
Glioma
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
Xiaolong Zhu
Hui Yang
Mengying Zhang
Xingwei Wu
Lan Jiang
Xiaocen Liu
Kun Lv
YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells
description Abstract Background Glioma is a common type of malignant brain tumor with a high mortality and relapse rate. The endosomal sorting complex required for transport (ESCRT) has been reported to be involved in tumorigenesis. However, the molecular mechanisms have not been clarified. Methods Bioinformatics was used to screen the ESCRT subunits highly expressed in glioma tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The function of the ESCRT subunits in glioma cells was examined in vitro. Transcriptome sequencing analyzed the target genes and signaling pathways affected by the ESCRT subunit. Finally, the relationship between m6A (N 6-methyladenosine) modification and high expression of the ESCRT subunit was studied. Results VPS25 was upregulated in glioma tissues, which was correlated with poor prognosis in glioma patients. Furthermore, VPS25 knockdown inhibited the proliferation, blocked the cell cycle, and promoted apoptosis in glioma cells. Meanwhile, VPS25 induced a G0/G1 phase arrest of the cell cycle in glioma cells by directly mediating p21, CDK2, and cyclin E expression, and JAK-signal transducer and activator of transcription (STAT) activation. Finally, YTHDC1 inhibited glioma proliferation by reducing the expression of VPS25. Conclusion These results suggest that VPS25 is a promising prognostic indicator and a potential therapeutic target for glioma.
format article
author Xiaolong Zhu
Hui Yang
Mengying Zhang
Xingwei Wu
Lan Jiang
Xiaocen Liu
Kun Lv
author_facet Xiaolong Zhu
Hui Yang
Mengying Zhang
Xingwei Wu
Lan Jiang
Xiaocen Liu
Kun Lv
author_sort Xiaolong Zhu
title YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells
title_short YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells
title_full YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells
title_fullStr YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells
title_full_unstemmed YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells
title_sort ythdc1-mediated vps25 regulates cell cycle by targeting jak-stat signaling in human glioma cells
publisher BMC
publishDate 2021
url https://doaj.org/article/68cd530934ee437c8d8f635e4d8b57f9
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AT huiyang ythdc1mediatedvps25regulatescellcyclebytargetingjakstatsignalinginhumangliomacells
AT mengyingzhang ythdc1mediatedvps25regulatescellcyclebytargetingjakstatsignalinginhumangliomacells
AT xingweiwu ythdc1mediatedvps25regulatescellcyclebytargetingjakstatsignalinginhumangliomacells
AT lanjiang ythdc1mediatedvps25regulatescellcyclebytargetingjakstatsignalinginhumangliomacells
AT xiaocenliu ythdc1mediatedvps25regulatescellcyclebytargetingjakstatsignalinginhumangliomacells
AT kunlv ythdc1mediatedvps25regulatescellcyclebytargetingjakstatsignalinginhumangliomacells
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