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.

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