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

• Published in: PloS one Vol. 15; no. 1; p. e0227634
• Main Authors: Yang, Li-Tao, Ma, Fei, Zeng, Hao-Tao, Zhao, Miao, Zeng, Xian-Hai, Liu, Zhi-Qiang, Yang, Ping-Chang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.01.2020; Public Library of Science (PLoS)
• Subjects: Adapters; Aged; Apoptosis; Apoptosis - physiology; Biochemistry; Biology and Life Sciences; Cancer cells; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell activation; Cell culture; Cisplatin; Comparative analysis; Decay; Defects; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epithelial Cells - metabolism; Epithelial Cells - pathology; Experiments; Fas Ligand Protein - genetics; Fas Ligand Protein - metabolism; FasL protein; Female; Flow cytometry; Gene expression; Gene Expression Regulation, Neoplastic; Health aspects; Humans; Immunology; Inducers; Laboratories; Ligands; Lipopolysaccharides; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medicine; Medicine and Health Sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Messenger RNA; Middle Aged; Mitogens; mRNA turnover; MyD88 protein; Novels; Pathogenesis; Physiology; Proteins; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - metabolism; Restoration; RNA; RNA Interference; RNA Stability; Signal transduction; Surgery; Toll-like receptors; Tumor Cells, Cultured; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0227634

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. 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. 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. 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.