ZEB1 induces non-small cell lung cancer development by targeting microRNA-320a to increase the expression of RAD51AP1

Exp Cell Res. 2021 Aug 15;405(2):112687. doi: 10.1016/j.yexcr.2021.112687. Epub 2021 Jun 5.

Abstract

Lung cancer is the most prevalent cancer worldwide, with its mortality rate reported to be in millions annually; one of the two subtypes is non-small cell lung cancer (NSCLC). In this study, we investigated the interactions and expressions of zinc finger E-box binding homeobox 1 (ZEB1), microRNA-320a (miR-320a) and RAD51-associated protein 1 (RAD51AP1) in NSCLC tissues to determine the roles of ZEB1 in regulation of miR-320a and RAD51AP1 in the development and metastasis of NSCLC. First, the expression levels of miR-320a and ZEB1 were quantified in NSCLC tissues and cells. Transfection assay was conducted to identify the effects of miR-320a on the progression of NSCLC cells. The interaction of miR-320a with ZEB1 and RAD51AP1 was predicted and verified using dual-luciferase reporter gene assay and chromatin immunoprecipitation assay. Finally, subcutaneous xenograft tumors of 6-week mice and metastatic model tumors of 8-week mice were established to further explore the in vivo effect of miR-320a/ZEB1/RAD51AP1 on NSCLC. The findings revealed a lower expression of miR-320a in NSCLC tissues and cells, while this result was reversed regarding ZEB1 expression. ZEB1 suppressed miR-320a expression and upregulation of miR-320a resulted in the reduction of proliferation, invasion and metastasis rate of NSCLC cells, and promoted NSCLC cell apoptosis. ZEB1 promoted the expression of RAD51AP1 via inhibition of miR-320a, promoting tumor growth in vivo. ZEB1 transcriptionally inhibited the expression of miR-320a and upregulated the expression of RAD51AP1, thereby promoting metastasis in NSCLC.

Keywords: Non-small cell lung cancer; RAD51AP1; ZEB1; miR-320a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice, SCID
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • RNA-Binding Proteins / metabolism*
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • DNA-Binding Proteins
  • MIRN320 microRNA, human
  • MicroRNAs
  • RAD51AP1 protein, human
  • RNA-Binding Proteins
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1