1. Academic Validation
  2. The IRF2/CENP-N/AKT signaling axis promotes proliferation, cell cycling and apoptosis resistance in nasopharyngeal carcinoma cells by increasing aerobic glycolysis

The IRF2/CENP-N/AKT signaling axis promotes proliferation, cell cycling and apoptosis resistance in nasopharyngeal carcinoma cells by increasing aerobic glycolysis

  • J Exp Clin Cancer Res. 2021 Dec 10;40(1):390. doi: 10.1186/s13046-021-02191-3.
Cheng-Lin Qi  # 1 Mao-Ling Huang  # 1 You Zou  # 1 Rui Yang 1 Yang Jiang 1 Jian-Fei Sheng 1 Yong-Gang Kong 1 Ze-Zhang Tao 1 2 Hong-Yan Feng 3 Qing-Quan Hua 1 2 Li-Hong Bu 4 Shi-Ming Chen 5 6
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei, 430060, P.R. China.
  • 2 Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei, 430060, P.R. China.
  • 3 PET-CT/MRI Center, Molecular Imaging Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
  • 4 PET-CT/MRI Center, Molecular Imaging Center, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China. bulihongs@whu.edu.cn.
  • 5 Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei, 430060, P.R. China. shimingchen0468@163.com.
  • 6 Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei, 430060, P.R. China. shimingchen0468@163.com.
  • # Contributed equally.
Abstract

Background: Centromere protein N (CENP-N) has been reported to be highly expressed in malignancies, but its role and mechanism in nasopharyngeal carcinoma (NPC) are unknown.

Methods: Abnormal CENP-N expression from NPC microarrays of GEO database was analyzed. CENP-N expression level was confirmed in NPC tissues and cell lines. Stable CENP-N knockdown and overexpression NPC cell lines were established, and transcriptome Sequencing after CENP-N knockdown was performed. In vitro and in vivo experiments were performed to test the impact of CENP-N knockdown in NPC cells. ChIP and dual luciferase reporter assays were used to verify the combination of IRF2 and CENP-N. Western blot analysis, cellular immunofluorescence, immunoprecipitation and GST pulldown assays were used to verify the combination of CENP-N and Akt.

Results: CENP-N was confirmed to be aberrantly highly expressed in NPC tissues and cell lines and to be associated with high 18F-FDG uptake in Cancer nests and poor patient prognosis. Transcriptome Sequencing after CENP-N knockdown revealed that genes with altered expression were enriched in pathways related to glucose metabolism, cell cycle regulation. CENP-N knockdown inhibited glucose metabolism, cell proliferation, cell cycling and promoted Apoptosis. IRF2 is a transcription factor for CENP-N and directly promotes CENP-N expression in NPC cells. CENP-N affects the glucose metabolism, proliferation, cell cycling and Apoptosis of NPC cells in vitro and in vivo through the Akt pathway. CENP-N formed a complex with Akt in NPC cells. Both an Akt Inhibitor (MK-2206) and a LDHA inhibitor (GSK2837808A) blocked the effect of CENP-N overexpression on NPC cells by promoting aerobic glycolysis, proliferation, cell cycling and Apoptosis resistance.

Conclusions: The IRF2/CENP-N/Akt axis promotes malignant biological behaviors in NPC cells by increasing aerobic glycolysis, and the IRF2/CENP-N/Akt signaling axis is expected to be a new target for NPC therapy.

Keywords

AKT; Aerobic glycolysis; CENP-N; Gglucose metabolism; IRF2; NPC.

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