Particulate matters 2.5 induce tumor progression in lung cancer by increasing the activity of hnRNPA2B1 resulting in retarding mRNA decay of oxidative phosphorylation

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
IUBMB Life Pub Date : 2024-03-07 DOI:10.1002/iub.2813
Wen Bian, Haifeng Yu, Xiaofei Zhang, Yuxuan Wang, Bin Ni
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引用次数: 0

Abstract

Particulate matter 2.5 (PM2.5) has been implicated in lung injury and various cancers, yet its precise mechanistic role remains elusive. To elucidate the key signaling pathways underpinning PM2.5-induced lung cancer progression, we embarked on a study examining the impact of PM2.5 both in vitro and in vivo. Lung cancer cell lines, A549 and H157, were employed for the in vitro investigations. Overexpression or knockdown techniques targeting the hnRNPA2B1 protein were implemented. Lung cancer cells were treated with a medium containing PM2.5 and subsequently prepared for in vitro evaluations. Cell growth, invasion, and migration were gauged using transwell and CCK-8 assays. Apoptosis was ascertained through flow cytometry and western blotting of pertinent proteins. Seahorse analyses probed the influence of PM2.5 on lung cancer energy metabolism. The RNA stability assay was employed to discern the impact of PM2.5 on the stability of oxidative phosphorylation-related genes in lung cancer. Our findings revealed that PM2.5 augmented cell proliferation, migration, and invasion rates. Similarly, a diminished apoptosis rate was observed in PM2.5-treated cells. Elevated expression of hnRNPA2B1 was detected in lung cancer cells exposed to PM2.5. Moreover, in cells treated with PM2.5, hnRNPA2B1 knockdown markedly curtailed cell proliferation by inducing G1–S cell cycle arrest and bolstered lung cancer cell apoptosis in vitro; it also curbed xenograft tumor growth. Mechanistically, our data suggest that PM2.5 undermines the stability of mRNA transcripts associated with oxidative phosphorylation (OXPHOS) and augments the formation of processing bodies (P-bodies), leading to an upsurge in OXPHOS levels. In conclusion, PM2.5 appears to drive lung cancer progression and migration by modulating the energy metabolism of lung cancer in a hnRNPA2B1-dependent manner.

颗粒物 2.5 通过增加 hnRNPA2B1 的活性,从而延缓氧化磷酸化的 mRNA 衰减,诱导肺癌的肿瘤进展。
颗粒物 2.5(PM2.5)与肺损伤和各种癌症有牵连,但其确切的机理作用仍然难以捉摸。为了阐明PM2.5诱导肺癌进展的关键信号通路,我们开始了一项研究,在体外和体内检测PM2.5的影响。体外研究采用了肺癌细胞系 A549 和 H157。采用了针对 hnRNPA2B1 蛋白的过表达或基因敲除技术。用含有 PM2.5 的培养基处理肺癌细胞,然后准备进行体外评估。细胞的生长、侵袭和迁移是通过Transwell和CCK-8测定法来衡量的。细胞凋亡则通过流式细胞仪和相关蛋白的 Western 印迹来确定。海马分析探究了 PM2.5 对肺癌能量代谢的影响。采用 RNA 稳定性分析法来确定 PM2.5 对肺癌中氧化磷酸化相关基因稳定性的影响。我们的研究结果表明,PM2.5 增加了细胞的增殖、迁移和侵袭率。同样,在经 PM2.5 处理的细胞中观察到凋亡率降低。在暴露于 PM2.5 的肺癌细胞中检测到 hnRNPA2B1 的表达升高。此外,在经PM2.5处理的细胞中,敲除hnRNPA2B1可通过诱导G1-S细胞周期停滞而显著抑制细胞增殖,并促进体外肺癌细胞凋亡;它还能抑制异种移植肿瘤的生长。从机理上讲,我们的数据表明,PM2.5 破坏了与氧化磷酸化(OXPHOS)相关的 mRNA 转录本的稳定性,并促进了加工体(P-bodies)的形成,从而导致 OXPHOS 水平的飙升。总之,PM2.5似乎以依赖hnRNPA2B1的方式调节肺癌的能量代谢,从而推动肺癌的进展和迁移。
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
IUBMB Life
IUBMB Life 生物-生化与分子生物学
CiteScore
10.60
自引率
0.00%
发文量
109
审稿时长
4-8 weeks
期刊介绍: IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.
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