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

Mal的恢复克服了肺癌细胞凋亡的缺陷。

  • 影响因子:3.02
  • DOI:10.1371/journal.pone.0227634
  • 作者列表:"Yang LT","Ma F","Zeng HT","Zhao M","Zeng XH","Liu ZQ","Yang PC
  • 发表时间:2020-01-24
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.

摘要

背景与目的: 癌症是威胁人类生命的疾病之一,其发病机制有待进一步研究。Toll样受体 (TLR) 活性参与细胞凋亡调控。本研究旨在阐明Mal (MyD88-adapter-like) 分子在肺癌 (LC) 细胞凋亡调控中的作用。 方法: 收集LC患者的LC组织。从组织中分离LC细胞和正常对照 (NC) 细胞,并通过相关的生物化学和免疫学方法进行分析。 结果: 我们发现与NC细胞相比,顺铂在培养物中诱导凋亡的LC细胞较少。Fas配体 (FasL) 在LC细胞中的表达低于NC细胞。LC细胞中faslmrna水平自发下降。在LC细胞中检测到FasL/TDP-43 的复合物。LC细胞比NC细胞表达更少的Mal。脂多糖 (LPS) 对Mal的激活增加了LC细胞中TDP-43 的表达。TDP-43 与FasL mRNA形成复合物,阻止FasL mRNA的衰变。Mal或TDP-43 的重建恢复了LC细胞对凋亡诱导剂的敏感性。 结论: LC细胞表达低水平的Mal,其通过损害faslmrna的表达而导致TDP-43 衰变。Mal的重建恢复了LC细胞对凋亡诱导剂的敏感性,这可能是LC治疗的一种新的治疗方法。

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影响因子:6.93
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DOI:10.1002/ijc.32530
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肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

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