PDLIM2 acts as a cancer suppressor gene in non-small cell lung cancer via the down regulation of NF-κB signaling

Mol Cell Probes. 2020 Oct:53:101628. doi: 10.1016/j.mcp.2020.101628. Epub 2020 Jul 1.

Abstract

PDZ and LIM domain containing protein 2 (PDLIM2) has been identified as a vital tumor-associated gene that is aberrantly expressed in various types of tumors. Yet, the involvement of PDLIM2 in non-small cell lung cancer (NSCLC) is currently undetermined. The design of the current study was to evaluate whether PDLIM2 plays a role in NSCLC. We found that PDLIM2 expression was commonly decreased in NSCLC tissues. Moreover, low expression of PDLIM2 was also detected in NSCLC cell lines and demethylation treatment restored PDLIM2 expression. The re-expression of PDLIM2 impeded the proliferative, colony-forming, and invasive capabilities of NCLCL cells. In contrast, depletion of PDLIM2 markedly enhanced the malignant behaviors of NSCLC cells. Notably, PDLIM2 overexpression downregulated the expression of nuclear factor (NF)-κB p65 subunit and repressed NF-κB transcription reporter activity in NSCLC cells. The overexpression of p65 significantly reversed PDLIM2-mediated antitumor effects in NSCLC cells. Additionally, the Xenograft tumor formation assay revealed that the overexpression of PDLIM2 markedly restricted the tumor growth of NSCLC in vivo. Overall, our study confirms that PDLIM2 acts as a tumor-inhibitor in NSCLC through the inactivation of NF-κB, suggesting PDLIM2 as a candidate therapeutic target for NSCLC.

Keywords: Invasion; NF-κB; NSCLC; PDLIM2; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • LIM Domain Proteins / genetics*
  • LIM Domain Proteins / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism*
  • NF-kappa B / metabolism
  • Neoplasm Transplantation
  • Signal Transduction

Substances

  • LIM Domain Proteins
  • Microfilament Proteins
  • NF-kappa B
  • PDLIM2 protein, human