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

Autoři: Li-Tao Yang aff001;  Fei Ma aff001;  Hao-Tao Zeng aff001;  Miao Zhao aff001;  Xian-Hai Zeng aff001;  Zhi-Qiang Liu aff001;  Ping-Chang Yang aff001
Působiště autorů: ENT Institute, Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China aff001;  Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article


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.


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.

Klíčová slova:

Apoptosis – Cancer treatment – Gene expression – Lung and intrathoracic tumors – Pathogenesis – RNA interference – RNA-binding proteins – Toll-like receptors


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