Open AccessRestoration of Mal overcomes the defects of apoptosis in lung cancer cells
Author(s) -
Litao Yang,
Fei Ma,
Hao-Tao Zeng,
Miao Zhao,
Xianhai Zeng,
Zhiqiang Liu,
PingChang Yang
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0227634
Subject(s) - fas ligand , apoptosis , cancer cell , biology , microbiology and biotechnology , cancer research , cell culture , inducer , immunology , chemistry , programmed cell death , cancer , gene , biochemistry , genetics
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.