SWI/SNF Complex Gene Mutations Promote the Liver Metastasis of Non-small Cell Lung Cancer Cells in NSI Mice

背景与目的 SWI/SNF复合体（switch/sucrose nonfermentable chromatin-remodeling complex, SWI/SNF）是一种重要的染色质重塑复合物，其亚基变异在多种肿瘤中存在，并与多种肿瘤细胞生物学特征相关。但其基因突变是否参与非小细胞肺癌（non-small cell lung cancer, NSCLC）肝转移过程尚不清楚。本研究拟探究SWI/SNF复合体基因突变对NSCLC肝转移的影响及潜在机制。方法 我们使用全外显子组测序（whole-exome sequencing, WES）分析了NSCLC细胞H1299、H23和H460中SWI...

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Published in:Zhongguo fei ai za zhi 2023-10, Vol.26 (10), p.753-764
Main Authors: GAO, Lingling, XIE, Zhi, LIN, Shouheng, LV, Zhiyi, ZHOU, Wenbin, CHEN, Ji, ZHU, Linlin, ZHANG, Li, ZENG, Penghui, HUANG, Xiaodan, YAN, Wenqing, CHEN, Yu, LU, Danxia, ZHANG, Shuilian, GUO, Weibang, LI, Peng, ZHANG, Xuchao
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Language:Chinese
Subjects:
Apolipoproteins
Cell cycle
Dehydrogenases
Enzymes
Gene expression
Immunohistochemistry
Liver
Lung cancer
lung neoplasms
Medical prognosis
Metastasis
Mutation
neoplasm metastasis
Protein expression
Proteins
swi/snf complex
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container_issue 10
container_start_page 753
container_title Zhongguo fei ai za zhi
container_volume 26
creator GAO, Lingling
XIE, Zhi
LIN, Shouheng
LV, Zhiyi
ZHOU, Wenbin
CHEN, Ji
ZHU, Linlin
ZHANG, Li
ZENG, Penghui
HUANG, Xiaodan
YAN, Wenqing
CHEN, Yu
LU, Danxia
ZHANG, Shuilian
GUO, Weibang
LI, Peng
ZHANG, Xuchao
description 背景与目的 SWI/SNF复合体（switch/sucrose nonfermentable chromatin-remodeling complex, SWI/SNF）是一种重要的染色质重塑复合物，其亚基变异在多种肿瘤中存在，并与多种肿瘤细胞生物学特征相关。但其基因突变是否参与非小细胞肺癌（non-small cell lung cancer, NSCLC）肝转移过程尚不清楚。本研究拟探究SWI/SNF复合体基因突变对NSCLC肝转移的影响及潜在机制。方法 我们使用全外显子组测序（whole-exome sequencing, WES）分析了NSCLC细胞H1299、H23和H460中SWI/SNF复合体基因突变。通过CRISPR/Cas9（clustered regularly interspaced short palindromic repeats）技术构建了ARID1A基因稳定敲除的H1299细胞株，建立了小鼠模型模拟NSCLC肝转移，观察不同基因突变对肝转移的影响。利用RNA-Seq和蛋白印迹分析差异基因的表达，并通过免疫组化技术（immunohistochemistry, IHC）检测了SWI/SNF复合体调控的靶分子在小鼠肝转移灶中的表达。结果 WES分析确定了SWI/SNF复合体基因的突变情况。动物实验结果显示SWI/SNF复合体基因突变与免疫缺陷小鼠较高的肝转移率相关。转录组测序和蛋白印迹分析显示SWI/SNF复合体基因突变细胞中ALDH1A1和APOBEC3B表达上调，尤其是ARID1A蛋白缺失的H460和H1299 sgARID1A中ALDH1A1表达水平显著上升。IHC染色亦显示H460和H1299 sgARID1A细胞肝转移灶中ALDH1A1高表达。结论 本研究强调了SWI/SNF复合体基因ARID1A和SMARCA4等突变在促进肺癌细胞肝转移中的关键作用。这些基因突变可能通过促进ALDH1A1与APOBEC3B高表达进而发挥肝特异性转移的作用，为深入探究肺癌肝转移分子机制提供了新线索。Background and objective The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the gen
doi_str_mv 10.3779/j.issn.1009-3419.2023.102.35
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1999-6187
language chi
recordid cdi_doaj_primary_oai_doaj_org_article_f618cd99a744487b9bb238ce05c00422
source Open Access: PubMed Central; Publicly Available Content Database
subjects Apolipoproteins
Cell cycle
Dehydrogenases
Enzymes
Gene expression
Immunohistochemistry
Liver
Lung cancer
lung neoplasms
Medical prognosis
Metastasis
Mutation
neoplasm metastasis
Protein expression
Proteins
swi/snf complex
title SWI/SNF Complex Gene Mutations Promote the Liver Metastasis of Non-small Cell Lung Cancer Cells in NSI Mice
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