Downregulation of GADD45B and PMAIP1 Mediated by TFAP2C Promotes Cell Proliferation in Non‐small Cell Lung Cancer Cells

Abstract

Non‐small cell lung cancer (NSCLC) is one of the main causes of death worldwide. At early stage, NSCLC can be treated with positive prognosis, but the limitation of biomarkers makes early diagnosis of lung cancer difficult. To identify lung cancer‐related biomarkers, we focused on the role of transcription factor TFAP2C as oncogene in lung cancer. In this study, microarray data were analyzed to identify tumor suppressor genes and 9 genes were screened for downregulation by TFAP2C. Of the 9 genes, growth arrest and DNA‐damage‐inducible beta (GADD45B) and phorbol‐12‐myristate‐13‐acetate‐induced protein 1 (PMAIP1) were selected as promising candidates for tumor suppressor genes downregulated by TFAP2C. When TFAP2C was overexpressed in NSCLC cells, the expressions of GADD45B and PMAIP1 at mRNA and protein levels were inhibited. In addition, GADD45B and PMAIP1 with downregulated by TFAP2C contributed to induction of cell proliferation and cell motility in NSCLC cells. Altogether, this study showed that GADD45B and PMAIP1 can act as tumor suppressors in NSCLC and can be used as useful markers in NSCLC therapy.Support or Funding InformationThis work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2019R1C1C1009423).