Dysregulation of ferroptosis may involve in the development of non-small-cell lung cancer in Xuanwei area.

Dysregulation of ferroptosis may involve in the development of non-small-cell lung cancer in Xuanwei area.
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铁凋亡失调可能参与宣威地区非小细胞肺癌的发生发展。

DOI:
10.1111/jcmm.16318
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发表时间:
2021-03
影响因子:
5.3
通讯作者:
Huang Y
Huang Y
中科院分区:
医学2区
文献类型:
--
作者:
Li G;Yang J;Zhao G;Shen Z;Yang K;Tian L;Zhou Q;Chen Y;Huang Y

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中国云南省宣威地区是全球肺癌发病率和死亡率最高的地区之一。当地居民多使用烟煤作为生活燃料,导致室内空气污染严重,并被确定为主要致癌物。当地政府开展炉灶改造工作后,居民肺癌发病率和死亡率居高不下。我们在此想知道该领域非小细胞肺癌(NSCLC)的发展是否存在蛋白质水平的特定机制。我们调查了宣威地区患者肿瘤中蛋白质谱的变化。采用串联质量标签(TMT)筛选癌组织和癌旁组织之间的差异蛋白。我们总共鉴定了 422 个差异表达蛋白,其中与癌旁组织相比,其中 162 个蛋白显着上调,260 个蛋白显着下调。许多差异表达的蛋白质与细胞外基质 (ECM) 受体相互作用、粘着斑、PI3K/AKT 通路和铁死亡有关。对硫氧还蛋白2(TXN2)和触珠蛋白(HP)这两种差异蛋白的进一步实验表明,它们表达的改变可以使肺癌细胞系对体外erastin或RSL诱导的铁死亡更具抵抗力,并促进裸鼠肿瘤的生长。总之,本研究揭示宣威地区肺癌的发生可能与铁死亡的异常调控有关。
The Xuanwei area of Yunnan Province, China, is one of the regions suffering from the highest occurrence and mortality rate of lung cancer in the world. Local residents tend to use bituminous coal as domestic fuel, which causes serious indoor air pollution and is established as the main carcinogen. After the local government carried out furnace and stove reform work, lung cancer rate including incidence and mortality among residents remains high. We herein wonder if there are specific mechanisms at protein level for the development of non‐small‐cell lung cancer (NSCLC) in this area. We investigated the changes of protein profiling in tumour of the patients from Xuanwei area. Tandem mass tag (TMT) was employed to screen the differential proteins between carcinoma and para‐carcinoma tissues. We identified a total of 422 differentially expressed proteins, among which 162 proteins were significantly up‐regulated and 260 were downregulated compared to para‐carcinoma tissues. Many of the differentially expressed proteins were related to extracellular matrix (ECM)‐receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, thioredoxin 2 (TXN2) and haptoglobin (HP), showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL‐induced ferroptosis in vitro, and promote the growth of tumour in nude mice. In conclusion, this study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.
DOI: 10.1016/j.cell.2012.03.042
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