ERGIC3, which is regulated by miR-203a, is a potential biomarker for non-small cell lung cancer

Cancer Sci. 2015 Oct;106(10):1463-73. doi: 10.1111/cas.12741. Epub 2015 Aug 10.

Abstract

In a previous study, we found that ERGIC3 was a novel lung cancer-related gene by screening libraries of differentially expressed genes. In this study, we developed a new murine monoclonal antibody (mAb) against ERGIC3. This avid antibody (6-C4) is well suited for immunohistochemistry, immunoblotting and solid-phase immunoassays. Furthermore, we systematically investigated expressions of ERGIC3 in a broad variety of normal human tissues and various types of tumors by immunohistochemistry. In normal human tissues, 6-C4 reacted only in some epithelial cells, such as hepatocytes, gastrointestinal epithelium, ducts and acini of the pancreas, proximal and distal tubules of the kidney, and mammary epithelial cells; however, most normal human tissues were not stained. Moreover, almost all carcinomas that originated from the epithelial cells were positive for 6-C4, whereas all sarcomas were negative. Notably, 6-C4 strongly stained non-small cell lung cancer (NSCLC) cells but did not react with normal lung tissues. Hence, ERGIC3 mAb could be used in histopathological diagnosis and cytopathological testing to detect early-stage NSCLC. We also studied the mechanisms of ERGIC3 regulation in vitro and in vivo by means of bioinformatics analysis, luciferase reporter assay, miRNA expression profiling and miRNA transfection. Results showed that miR-203a downregulation induced ERGIC3 overexpression in NSCLC cells.

Keywords: Biomarker; ERGIC3; miR-203a; monoclonal antibody; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • Down-Regulation / genetics
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • ERGIC3 protein, human
  • MIRN203 microRNA, human
  • Membrane Proteins
  • MicroRNAs