Restoration of Mal overcomes the defects of apoptosis in lung cancer cells

PLoS One. 2020 Jan 24;15(1):e0227634. doi: 10.1371/journal.pone.0227634. eCollection 2020.

Abstract

Background and aims: Cancer is one of the life-threatening diseases of human beings; the pathogenesis of cancer remains to be further investigated. Toll like receptor (TLR) activities are involved in the apoptosis regulation. This study aims to elucidate the role of Mal (MyD88-adapter-like) molecule in the apoptosis regulation of lung cancer (LC) cells.

Methods: The LC tissues were collected from LC patients. LC cells and normal control (NC) cells were isolated from the tissues and analyzed by pertinent biochemical and immunological approaches.

Results: We found that fewer apoptotic LC cells were induced by cisplatin in the culture as compared to NC cells. The expression of Fas ligand (FasL) was lower in LC cells than that in NC cells. FasL mRNA levels declined spontaneously in LC cells. A complex of FasL/TDP-43 was detected in LC cells. LC cells expressed less Mal than NC cells. Activation of Mal by lipopolysaccharide (LPS) increased TDP-43 expression in LC cells. TDP-43 formed a complex with FasL mRNA to prevent FasL mRNA from decay. Reconstitution of Mal or TDP-43 restored the sensitiveness of LC cells to apoptotic inducers.

Conclusions: LC cells express low Mal levels that contributes to FasL mRNA decay through impairing TDP-43 expression. Reconstitution of Mal restores sensitiveness of LC cells to apoptosis inducers that may be a novel therapeutic approach for LC treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Aged
  • Apoptosis / physiology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Fas Ligand Protein / genetics*
  • Fas Ligand Protein / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • RNA Interference
  • RNA Stability
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism*
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Receptors, Interleukin-1
  • TARDBP protein, human
  • TIRAP protein, human

Grants and funding

This study was supported by grants of Dr. Ping-Chang Yang from National Natural Science Foundation of China (31570932), Shenzhen Science, Technology and Innovation Committee (KQJSCX20180328095619081, KQTD20170331145453160), and Guangdong Provincial Key Laboratory of Regional Immunity and Diseases (2019B030301009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.