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都铎葡萄球菌核酸酶通过调节S100A11驱动非小细胞肺癌细胞的化学抗性。

Tudor staphylococcal nuclease drives chemoresistance of non-small cell lung carcinoma cells by regulating S100A11.

作者信息

Zagryazhskaya Anna, Surova Olga, Akbar Nadeem S, Allavena Giulia, Gyuraszova Katarina, Zborovskaya Irina B, Tchevkina Elena M, Zhivotovsky Boris

机构信息

Institute of Environmental Medicine, Division of Toxicology, Stockholm, Sweden.

Ludwig Institute for Cancer Research Ltd, Karolinska Institutet, Stockholm, Sweden.

出版信息

Oncotarget. 2015 May 20;6(14):12156-73. doi: 10.18632/oncotarget.3495.

DOI:10.18632/oncotarget.3495
PMID:25940438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4494929/
Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC), the major lung cancer subtype, is characterized by high resistance to chemotherapy. Here we demonstrate that Tudor staphylococcal nuclease (SND1 or TSN) is overexpressed in NSCLC cell lines and tissues, and is important for maintaining NSCLC chemoresistance. Downregulation of TSN by RNAi in NSCLC cells led to strong potentiation of cell death in response to cisplatin. Silencing of TSN was accompanied by a significant decrease in S100A11 expression at both mRNA and protein level. Downregulation of S100A11 by RNAi resulted in enhanced sensitivity of NSCLC cells to cisplatin, oxaliplatin and 5-fluouracil. AACOCF(3), a phospholipase A(2) (PLA(2)) inhibitor, strongly abrogated chemosensitization upon silencing of S100A11 suggesting that PLA(2) inhibition by S100A11 governs the chemoresistance of NSCLC. Moreover, silencing of S100A11 stimulated mitochondrial superoxide production, which was decreased by AACOCF(3), as well as N-acetyl-L-cysteine, which also mimicked the effect of PLA(2) inhibitor on NSCLC chemosensitization upon S100A11 silencing. Thus, we present the novel TSN-S100A11-PLA(2) axis regulating superoxide-dependent apoptosis, triggered by platinum-based chemotherapeutic agents in NSCLC that may be targeted by innovative cancer therapies.

摘要

肺癌是全球癌症相关死亡的主要原因。非小细胞肺癌（NSCLC）是主要的肺癌亚型，其特点是对化疗具有高度抗性。在此我们证明，Tudor葡萄球菌核酸酶（SND1或TSN）在NSCLC细胞系和组织中过表达，并且对于维持NSCLC的化学抗性很重要。在NSCLC细胞中通过RNA干扰下调TSN导致对顺铂的细胞死亡强烈增强。TSN的沉默伴随着S100A11在mRNA和蛋白质水平的显著降低。通过RNA干扰下调S100A11导致NSCLC细胞对顺铂、奥沙利铂和5-氟尿嘧啶的敏感性增强。AACOCF(3)，一种磷脂酶A(2)（PLA(2)）抑制剂，在沉默S100A11后强烈消除化学增敏作用，表明S100A11对PLA(2)的抑制作用决定了NSCLC的化学抗性。此外，沉默S100A11刺激线粒体超氧化物产生，AACOCF(3)以及N-乙酰-L-半胱氨酸可降低这种产生，N-乙酰-L-半胱氨酸也模拟了PLA(2)抑制剂对沉默S100A11后的NSCLC化学增敏作用。因此，我们提出了由铂类化疗药物在NSCLC中触发的调节超氧化物依赖性凋亡的新型TSN-S100A11-PLA(2)轴，这可能是创新癌症治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/d363e23d0856/oncotarget-06-12156-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/9208cfd4bc26/oncotarget-06-12156-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/35cf7f8ec707/oncotarget-06-12156-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/5cbdc128c6b1/oncotarget-06-12156-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/94097575e356/oncotarget-06-12156-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/19f7dee03fe3/oncotarget-06-12156-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/dc2974557a62/oncotarget-06-12156-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/d363e23d0856/oncotarget-06-12156-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/9208cfd4bc26/oncotarget-06-12156-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/fdc2d15c8c3d/oncotarget-06-12156-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/35cf7f8ec707/oncotarget-06-12156-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/5cbdc128c6b1/oncotarget-06-12156-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/94097575e356/oncotarget-06-12156-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/19f7dee03fe3/oncotarget-06-12156-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/dc2974557a62/oncotarget-06-12156-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/4494929/d363e23d0856/oncotarget-06-12156-g008.jpg

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2
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Nat Commun. 2014 May 8;5:3795. doi: 10.1038/ncomms4795.
3
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Cell Death Discov. 2025 Jan 30;11(1):34. doi: 10.1038/s41420-025-02310-5.
4
Mechanisms Behind the Impact of PIWI Proteins on Cancer Cells: Literature Review.PIWI 蛋白影响癌细胞的作用机制：文献综述。
Int J Mol Sci. 2024 Nov 14;25(22):12217. doi: 10.3390/ijms252212217.
5
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J Proteome Res. 2023 Jun 2;22(6):1923-1935. doi: 10.1021/acs.jproteome.3c00045. Epub 2023 May 1.
6
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7
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9
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