Silencing of RAD51AP1 suppresses epithelial-mesenchymal transition and metastasis in non-small cell lung cancer

Thorac Cancer. 2019 Sep;10(9):1748-1763. doi: 10.1111/1759-7714.13124. Epub 2019 Jul 17.

Abstract

Background: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related mortality and is frequently accompanied by metastasis. The crucial roles of genes in lung cancer have attracted attention. Thus, this study aimed to investigate the effects of RAD51AP1 on the epithelial-mesenchymal transition (EMT) and metastasis of NSCLC.

Methods: The positive expression rate of the RAD51AP1 protein was examined. NSCLC cells were transfected with a series of plasmids to alter the expression of RAD51AP1 to clarify the influence of RAD51AP1 on EMT and metastasis in NSCLC, as well as NSCLC cell migration, invasion, apoptosis, proliferation, and cloning. An in vivo experiment was conducted to determine the oncogenicity of human NSCLC cells in nude mice.

Results: RAD51AP1 was highly expressed in NSCLC tissues. Furthermore, we found promotion of N-cadherin, vimentin, fibronectin, MMP-2, OPN, CD62, and TMP-2, but inhibition of E-cadherin, occludin, cytokeratin in the context of elevated RAD51AP1 expression. An in vivo experiment also confirmed that silencing of RAD51AP1 could inhibit NSCLC tumor formation and growth.

Conclusion: Our results revealed that RAD51AP1 silencing suppressed the EMT and metastasis of NSCLC, thereby highlighting its potential as a promising novel target for NSCLC treatment.

Keywords: Epithelial-mesenchymal transition; RAD51 associated protein 1; invasion; metastasis; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / prevention & control*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Cell Movement
  • Cell Proliferation
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epithelial-Mesenchymal Transition*
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Small Interfering / genetics*
  • RNA-Binding Proteins / antagonists & inhibitors*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • RAD51AP1 protein, human
  • RNA, Small Interfering
  • RNA-Binding Proteins