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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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) |
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YTHDC1 VPS25 Cell cycle JAK–STAT Glioma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 |
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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 |
work_keys_str_mv |
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1718371961261785088 |