Research Paper Volume 13, Issue 24 pp 26180—26200

NAP1L1 promotes proliferation and chemoresistance in glioma by inducing CCND1/CDK4/CDK6 expression through its interaction with HDGF and activation of c-Jun

Zigui Chen1,2, *, , Yingying Xie1,2, , Hongcheng Luo3, , Ye Song4, , Tianshi Que4, , Rentong Hu3, , Huatuo Huang3, , Kunxiang Luo5, , Chuanyu Li5, , Chengjian Qin5, , Chuanhua Zheng5, , Weiyi Fang1,2, , Longyang Liu1,2, , Hao Long1,4, , Qisheng Luo1,5, ,

  • 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
* First author

Received: September 7, 2021       Accepted: December 13, 2021       Published: December 27, 2021
How to Cite

Copyright: © 2021 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


NAP1L1: nucleosome assembly protein 1 Like 1; HDGF: hepatoma-derived growth factor; TCGA: the cancer genome atlas; OS: overall survival; RT-qPCR: real time quantitative polymerase chain reaction; TMA: tissue microarray; DFS: disease free survival; H&E: hematoxylin and eosin; KPS: Karnofsky Performance Status Scale.