NLRP1 inhibits lung adenocarcinoma growth through mediating mitochondrial dysregulation in an inflammasome-independent manner.

IF 1.9 4区 医学 Q2 BIOLOGY
Chen-Jing Lin, Guang-Ang Tian, Wen-Ya Zhao, Yi Tian, Yi-Ru Liu, Dian-Na Gu, Ling Tian
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引用次数: 0

Abstract

NLRP1, the first identified inflammasome-forming sensor, is thought to be involved in cancer, yet its definite function in lung adenocarcinoma (LUAD) remains unclear. Herein, we explored the expression and function of NLRP1 in LUAD. Decreased NLRP1 expression was identified in LUAD, which was associated with a poor prognosis. Overexpression of NLRP1 inhibited tumor growth in vitro and in vivo. Mechanically, this effect was observed regardless of inflammasome activation. Further studies revealed that overexpression of NLRP1 downregulated the phosphorylation of DRP1 and promoted mitochondrial fusion, which was mediated by inhibition of NF-κB activity. NF-κB agonist could neutralize the effect of NLRP1 on mitochondrial dynamics. In addition, LUAD sensitivity to cisplatin was enhanced by decreased mitochondrial fission resulting from up-regulated NLRP1. In conclusion, our findings demonstrated an unexpected role of NLRP1 in LUAD by modulating mitochondrial activities, which provides strong evidence for its potential in LUAD treatment.

NLRP1 通过介导线粒体失调,以炎性体外依赖的方式抑制肺腺癌的生长。
NLRP1是第一个被发现的炎性体形成传感器,被认为与癌症有关,但它在肺腺癌(LUAD)中的明确功能仍不清楚。在此,我们探讨了 NLRP1 在 LUAD 中的表达和功能。研究发现,NLRP1在LUAD中的表达减少与预后不良有关。NLRP1 的过表达抑制了肿瘤在体外和体内的生长。从机理上讲,无论炎性体是否激活,都能观察到这种效应。进一步的研究发现,NLRP1的过度表达会降低DRP1的磷酸化,促进线粒体融合,而这是通过抑制NF-κB的活性来实现的。NF-κB 激动剂可以中和 NLRP1 对线粒体动力学的影响。此外,NLRP1上调导致线粒体裂变减少,从而增强了LUAD对顺铂的敏感性。总之,我们的研究结果表明,NLRP1通过调节线粒体活性在LUAD中发挥了意想不到的作用,这为其在LUAD治疗中的潜力提供了有力证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.00
自引率
0.00%
发文量
129
审稿时长
2 months
期刊介绍: The Brazilian Journal of Medical and Biological Research, founded by Michel Jamra, is edited and published monthly by the Associação Brasileira de Divulgação Científica (ABDC), a federation of Brazilian scientific societies: - Sociedade Brasileira de Biofísica (SBBf) - Sociedade Brasileira de Farmacologia e Terapêutica Experimental (SBFTE) - Sociedade Brasileira de Fisiologia (SBFis) - Sociedade Brasileira de Imunologia (SBI) - Sociedade Brasileira de Investigação Clínica (SBIC) - Sociedade Brasileira de Neurociências e Comportamento (SBNeC).
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