SWI/SNF Complex Gene Mutations Promote the Liver Metastasis
of Non-small Cell Lung Cancer Cells in NSI Mice.
10.3779/j.issn.1009-3419.2023.102.35
- Author:
Lingling GAO
1
;
Zhi XIE
2
;
Shouheng LIN
3
;
Zhiyi LV
2
;
Wenbin ZHOU
2
;
Ji CHEN
1
;
Linlin ZHU
1
;
Li ZHANG
1
;
Penghui ZENG
1
;
Xiaodan HUANG
2
;
Wenqing YAN
2
;
Yu CHEN
2
;
Danxia LU
2
;
Shuilian ZHANG
2
;
Weibang GUO
2
;
Peng LI
3
;
Xuchao ZHANG
1
Author Information
1. Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
2. Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
3. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
- Publication Type:Journal Article
- Keywords:
Lung neoplasms;
Mutation;
Neoplasm metastasis;
SWI/SNF complex
- MeSH:
Animals;
Mice;
Carcinoma, Non-Small-Cell Lung/genetics*;
Lung Neoplasms/genetics*;
Mutation;
Liver Neoplasms/genetics*
- From:
Chinese Journal of Lung Cancer
2023;26(10):753-764
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex.
METHODS:The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases.
RESULTS:WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group.
CONCLUSIONS:This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
