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HNF4A-CHPF 通路通过与 MAD1L1 的相互作用促进胶质瘤的增殖和侵袭。

The HNF4A-CHPF pathway promotes proliferation and invasion through interactions with MAD1L1 in glioma.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.

Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi Province, China.

出版信息

Aging (Albany NY). 2023 Oct 17;15(20):11052-11066. doi: 10.18632/aging.205076.

DOI:10.18632/aging.205076
PMID:37851364
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10637790/
Abstract

Chondroitin polymerizing factor (CHPF) is an important glycosyltransferases that participates in the biosynthesis of chondroitin sulfate (CS). Our previous study showed that silencing CHPF expression inhibited glioma cell proliferation , but the molecular mechanisms by which CHPF contributes to development of glioma have not been characterized. In this study, we found that CHPF was up-regulated in glioma tissues and was positively correlated with malignant clinical pathological characteristics of patients with glioma. Silencing CHPF expression inhibited proliferation, colony formation, migration, and cell cycle of glioma cells. Moreover, silencing CHPF suppressed glioma malignance . Immunoprecipitation, co-immunoprecipitation, GST pulldown, and liquid chromatography-mass spectrometry (LC-MS/MS) assays were used to verify the interaction between CHPF and Mitotic arrest deficient 1-like 1 (MAD1L1). In addition, Chromatin Immunoprecipitation (ChIP)-PCR analysis showed that HNF4A bound to the CHPF promoter region, which indicated that the transcription factor hepatocyte nuclear factor 4A (HNF4A) could regulate the expression of CHPF in glioma cells.

摘要

软骨素聚合因子 (CHPF) 是一种重要的糖基转移酶，参与硫酸软骨素 (CS) 的生物合成。我们之前的研究表明，沉默 CHPF 表达抑制神经胶质瘤细胞增殖，但是 CHPF 促进神经胶质瘤发生的分子机制尚未阐明。在这项研究中，我们发现 CHPF 在神经胶质瘤组织中上调，并且与神经胶质瘤患者恶性临床病理特征呈正相关。沉默 CHPF 表达抑制神经胶质瘤细胞的增殖、集落形成、迁移和细胞周期。此外，沉默 CHPF 抑制神经胶质瘤的恶性程度。免疫沉淀、共免疫沉淀、GST 下拉和液相色谱-质谱联用 (LC-MS/MS) 分析用于验证 CHPF 与有丝分裂阻滞缺陷 1 样 1 (MAD1L1) 之间的相互作用。此外，染色质免疫沉淀 (ChIP)-PCR 分析表明，转录因子肝细胞核因子 4A (HNF4A) 结合到 CHPF 启动子区域，这表明 HNF4A 可以调节神经胶质瘤细胞中 CHPF 的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/c842c4358fd3/aging-15-205076-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/87e463f90145/aging-15-205076-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/887c8758c3e6/aging-15-205076-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/01962f14fbf6/aging-15-205076-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/8033f45358bd/aging-15-205076-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/8b9ee75d641f/aging-15-205076-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/c842c4358fd3/aging-15-205076-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/87e463f90145/aging-15-205076-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/887c8758c3e6/aging-15-205076-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/01962f14fbf6/aging-15-205076-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/8033f45358bd/aging-15-205076-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/8b9ee75d641f/aging-15-205076-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d5d/10637790/c842c4358fd3/aging-15-205076-g006.jpg

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