XB130, regulated by miR-203, miR-219, and miR-4782-3p, mediates the proliferation and metastasis of non-small-cell lung cancer cells

Mol Carcinog. 2020 May;59(5):557-568. doi: 10.1002/mc.23180. Epub 2020 Mar 11.

Abstract

XB130 is a novel adapter protein that behaves as a tumor promoter or suppressor mediating cell proliferation and metastasis in the development of different human tumors. Altered expression of XB130 has been verified in human non-small cell-lung cancer (NSCLC). However, the exact effect of XB130 on NSCLC is not well-understood. In this study, we investigated the biological function and posttranscriptional regulation of XB130 in NSCLC. First, the effects of XB130 silence on NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were examined. Then the targeting relationship between XB130 and miR-203, miR-219, or miR-4782-3p was demonstrated by dual-luciferase reporter assay. Finally, the effects of miR-203, miR-219, and miR-4782-3p on NSCLC cell function were studied, respectively. We found that XB130 silence significantly inhibited cell growth, migration and invasion, and reversed EMT. Furthermore, XB130 was posttranscriptionally regulated by miR-203, miR-219, and miR-4782-3p. Overexpression of miR-203, miR-219, or miR-4782-3p inhibited cell growth, migration and invasion, and reversed EMT, just like the role of XB130 in NSCLC cells, whereas the suppressive effects of microRNA (miRNA) overexpression were weakened by miRNA inhibitors or ectopic expression of XB130 in NSCLC cells. These data demonstrate that XB130 is posttranscriptionally regulated by miR-203, miR-219, and miR-4782-3p and mediates the proliferation and metastasis of NSCLC cells.

Keywords: EMT; XB130; adapter protein; cell growth; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Cell Movement*
  • Cell Proliferation*
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • MicroRNAs / genetics*
  • Tumor Cells, Cultured

Substances

  • AFAP1L2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • MIRN203 microRNA, human
  • MIRN219 microRNA, human
  • MicroRNAs