Etoposide induced NMI promotes cell apoptosis by activating the ARF-p53 signaling pathway in lung carcinoma

Dan Song; Jiabao Zhao; Chen Su; Ying Jiang; Jingjing Hou

doi:10.1016/j.bbrc.2017.10.010

Etoposide induced NMI promotes cell apoptosis by activating the ARF-p53 signaling pathway in lung carcinoma

Biochem Biophys Res Commun. 2018 Jan 1;495(1):368-374. doi: 10.1016/j.bbrc.2017.10.010. Epub 2017 Oct 10.

Authors

Dan Song¹, Jiabao Zhao², Chen Su³, Ying Jiang⁴, Jingjing Hou⁵

Affiliations

¹ State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
² Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian 361004, China.
³ Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian 361004, China; Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, China.
⁴ West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
⁵ State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian 361004, China; Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, China. Electronic address: jjhou@xmu.edu.cn.

PMID: 29030066
DOI: 10.1016/j.bbrc.2017.10.010

Abstract

Lung carcinoma is one of the leading causes of cancer-related death. The N-Myc and STATs interactor (NMI) has been reported to take participate in lots of physiological processes, but the involvement and functional mechanisms of NMI in lung carcinoma are poorly understood. In this study, we found that etoposide induces proliferation suppression, cell apoptosis and increases caspase-3 activity in A549 cells. Furthermore, etoposide treatment up-regulates the expression of NMI and ARF, enhances the interaction of NMI and ARF and promotes the p53 transcriptional activities. By contrast, when silencing NMI, the proliferation suppression and cell apoptosis caused by etoposide were repressed and the p53 signaling pathway activation was also suppressed. These investigations demonstrated etoposide-induced NMI can suppress tumor proliferation and promote cell apoptosis by activating the ARF-p53 signaling pathway in lung carcinoma. Our results provide an alternative mechanism for etoposide in lung carcinoma and suggest NMI has a critical role in suppressing lung carcinoma progression.

Keywords: ARF; Apoptosis; Etoposide; NMI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Antineoplastic Agents, Phytogenic / administration & dosage
Apoptosis / drug effects*
Biomarkers, Tumor / metabolism
Etoposide / administration & dosage*
Humans
Intracellular Signaling Peptides and Proteins / metabolism*
Lung Neoplasms / drug therapy*
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology
Signal Transduction / drug effects
Tumor Suppressor Protein p14ARF / metabolism*
Tumor Suppressor Protein p53 / metabolism*

Substances

Antineoplastic Agents, Phytogenic
Biomarkers, Tumor
Intracellular Signaling Peptides and Proteins
NMI protein, human
TP53 protein, human
Tumor Suppressor Protein p14ARF
Tumor Suppressor Protein p53
Etoposide