NAP1L1 promotes proliferation and chemoresistance in glioma by inducing CCND1/CDK4/CDK6 expression through its interaction with HDGF and activation of c-Jun.
机构：[1]Neuroscience Center, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.[2]Southern Medical University, Guangzhou, Guangdong 510000, China.[3]Department of Laboratory Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, Baise 53300, China.[4]Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.[5]Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, Baise 53300, China.
The prognosis of glioma is poor as its pathogenesis and mechanisms underlying cisplatin chemoresistance remain unclear. Nucleosome assembly protein 1 like 1 (NAP1L1) is regarded as a hallmark of malignant tumors. However, the role of NAP1L1 in glioma remains unknown. In this study, we aimed to investigate the molecular functions of NAP1L1 in glioma and its involvement in cisplatin chemoresistance, if any. NAP1L1 was found to be upregulated in samples from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry indicated that NAP1L1 and hepatoma-derived growth factor (HDGF) were enhanced in glioma as compared to the para-tumor tissues. High expressions of NAP1L1 and HDGF were positively correlated with the WHO grade, KPS, Ki-67 index, and recurrence. Moreover, NAP1L1 expression was also positively correlated with the HDGF expression in glioma tissues. Functional studies suggested that knocking down NAP1L1 could significantly inhibit glioma cell proliferation both in vitro and in vivo, as well as enhance the sensitivity of glioma cells to cisplatin (cDDP) in vitro. Mechanistically, NAP1L1 could interact with HDGF at the protein level and they co-localize in the cytoplasm. HDGF knockdown in NAP1L1-overexpressing glioma cells significantly inhibited cell proliferation. Furthermore, HDGF could interact with c-Jun, an oncogenic transcription factor, which eventually induced the expressions of cell cycle promoters, CCND1/CDK4/CDK6. This finding suggested that NAP1L1 could interact with HDGF, and the latter recruited c-Jun, a key oncogenic transcription factor, that further induced CCND1/CDK4/CDK6 expression, thereby promoting proliferation and chemoresistance in glioma cells. High expression of NAP1L1 in glioma tissues indicated shorter overall survival in glioma patients.
基金：
National Natural
Science Foundation of China (grant no. 81760450),
Natural Science Foundation of Guangxi Province (grant
no. 2017GXNSFAA198322, 2019GXNSFDA245034)
and The First Batch of High-level Talent Scientific
Research Projects of the Affiliated Hospital of Youjiang
Medical University for Nationalities in 2019 (grant no.
R20196310).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|2 区医学
小类|1 区老年医学3 区细胞生物学
最新[2025]版：
无
第一作者：
第一作者机构：[1]Neuroscience Center, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.[2]Southern Medical University, Guangzhou, Guangdong 510000, China.
通讯作者：
通讯机构：[1]Neuroscience Center, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.[2]Southern Medical University, Guangzhou, Guangdong 510000, China.[4]Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.[5]Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, Baise 53300, China.
推荐引用方式(GB/T 7714)：
Chen Zigui,Xie Yingying,Luo Hongcheng,et al.NAP1L1 promotes proliferation and chemoresistance in glioma by inducing CCND1/CDK4/CDK6 expression through its interaction with HDGF and activation of c-Jun.[J].Aging.2021,13(24):26180-26200.doi:10.18632/aging.203805.
APA：
Chen Zigui,Xie Yingying,Luo Hongcheng,Song Ye,Que Tianshi...&Luo Qisheng.(2021).NAP1L1 promotes proliferation and chemoresistance in glioma by inducing CCND1/CDK4/CDK6 expression through its interaction with HDGF and activation of c-Jun..Aging,13,(24)
MLA：
Chen Zigui,et al."NAP1L1 promotes proliferation and chemoresistance in glioma by inducing CCND1/CDK4/CDK6 expression through its interaction with HDGF and activation of c-Jun.".Aging 13..24(2021):26180-26200
医学