Epigenetic and transcriptional activation of the secretory kinase <i>FAM20C</i> as an oncogene in glioma

Bo Gong; Yi Liang; Qian Zhang; Huan Li; Jialing Xiao; Liang Wang; Han Chen; Wenjie Yang; Xiaoqing Wang; Yi Wang; Zongze He

doi:10.1016/j.jgg.2023.01.008

Volume 50 Issue 6

Jun. 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(6): 422-433

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Epigenetic and transcriptional activation of the secretory kinase FAM20C as an oncogene in glioma

doi: 10.1016/j.jgg.2023.01.008

a. Department of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China;
b. The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China;
c. Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China;
d. Department of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China;
e. Department of Pathology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China;
f. Department of Critical Care Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China

Funds:

This study was supported by the grants from Department of Science and Technology of Sichuan Province, China (No. 23ZDYF2212), Medico-Engineering Cooperation Funds from the University of Electronic Science and Technology of China (No. ZYGX2021YGLH209), the Department of Science and Technology of Sichuan Province (Nos. 2022NSFSC0760 and 2022JDTD0024), and the Chengdu Science and Technology Bureau (2022-YF05-01625-SN).

Received Date: 2022-10-27
Accepted Date: 2023-01-14
Rev Recd Date: 2023-01-03
Publish Date: 2023-01-25

Abstract

Abstract

Gliomas are the most prevalent and aggressive malignancies of the nervous system. Previous bioinformatic studies have revealed the crucial role of the secretory pathway kinase FAM20C in the prediction of glioma invasion and malignancy. However, little is known about the pathogenesis of FAM20C in the regulation of glioma. Here, we construct the full-length transcriptome atlas in paired gliomas and observe that 22 genes are upregulated by full-length transcriptome and differential APA analysis. Analysis of ATAC-seq data reveals that both FAM20C and NPTN are the hub genes with chromatin openness and differential expression. Further, in vitro and in vivo studies suggest that FAM20C stimulates the proliferation and metastasis of glioma cells. Meanwhile, NPTN, a novel cancer suppressor gene, counteracts the function of FAM20C by inhibiting both the proliferation and migration of glioma. The blockade of FAM20C by neutralizing antibodies results in the regression of xenograft tumors. Moreover, MAX, BRD4, MYC, and REST are found to be the potential trans-active factors for the regulation of FAM20C. Taken together, our results uncover the oncogenic role of FAM20C in glioma and shed new light on the treatment of glioma by abolishing FAM20C.
- Glioma,
- Alternative polyadenylation sites,
- FAM20C,
- Trans-active factors

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References(75)

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