c-myc-mediated upregulation of NAT10 facilitates tumor development via cell cycle regulation in non-small cell lung cancer.

Zimu Wang, Yicong Huang, Wanjun Lu, Jiaxin Liu, Xinying Li, Suhua Zhu, Hongbing Liu, Yong Song
Author Information
  1. Zimu Wang: Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
  2. Yicong Huang: Donald Bren School of Information and Computer Sciences, University of California, Irvine, USA.
  3. Wanjun Lu: Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
  4. Jiaxin Liu: Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
  5. Xinying Li: Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, 210008, Jiangsu, China.
  6. Suhua Zhu: Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
  7. Hongbing Liu: Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China. netlhb@126.com.
  8. Yong Song: Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China. yong.song@nju.edu.cn. ORCID

Abstract

N-acetyltransferase 10 (NAT10) is a nucleolar acetyltransferase and has been reported to facilitate tumorigenesis in various cancers, but its role in NSCLC and how it is regulated remain to be assessed. The expression of NAT10 was explored in online databases and our collected clinical specimens. The relationship of NAT10 and clinical characteristics was evaluated using the online databases. Functional analyses were utilized to determine the effect of NAT10 on the proliferation and migration abilities. KEGG pathway analyses were conducted to investigate NAT10-related pathways in NSCLC. The influence of NAT10 on cell cycle was assessed by flow cytometry and cell synchronization assay. The association between c-myc and NAT10 promoter was determined by ChIP. Compared with normal tissue, NAT10 was significantly overexpressed in NSCLC. Upregulated NAT10 was associated with more advanced stage for lung adenocarcinoma and shorter overall survival and first progression time for lung cancer. NAT10 could promote proliferation and migration of NSCLC cells in vitro. c-myc positively regulated the expression of NAT10 as a transcription factor. KEGG pathway analyses indicated that NAT10 was significantly involved in cell cycle regulation, cytokine-cytokine receptor interaction and other pathways. The knockdown of NAT10-induced G1 arrest, which was possibly mediated by the downregulation of cyclin D1.Our findings suggested that c-myc-mediated upregulation of NAT10 promoted the proliferation and migration of NSCLC cells and NAT10 might be a marker for prognosis and a promising target for treatment in NSCLC.

Keywords

References

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Grants

  1. 81770082/National Natural Science Foundation of China
  2. BE2019719/Natural Science Foundation of Jiangsu Province

MeSH Term

Acetyltransferases
Carcinoma, Non-Small-Cell Lung
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
N-Terminal Acetyltransferases
Proto-Oncogene Proteins c-myc
Up-Regulation

Chemicals

MYC protein, human
Proto-Oncogene Proteins c-myc
Acetyltransferases
N-Terminal Acetyltransferases
NAT10 protein, human

Word Cloud

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