NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway

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Abstract

Background

Lung cancer has the highest case fatality rate among cancers because of uncontrolled proliferation and early metastasis of cancer cells in the lung tissue. This study aimed to clarify the role of the non-SMC condensin I complex, subunit G (NCAPG) in lung adenocarcinoma (LUAD), explore the mechanisms of its progression, and lay the foundation for the search for new biological markers.

Methods

We analyzed overlapping differentially expressed genes (DEGs) from three datasets; a protein–protein interaction (PPI) network was subsequently constructed and analyzed using Cytoscape. We then selected NCAPG for validation because of its poor prognosis and because it has not been sufficiently studied in the context of LUAD. Immunohistochemical analysis was used to detect the expression of NCAPG in LUAD tissues, and the relationships between NCAPG and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to verify the role of NCAPG in LUAD. Finally, we studied the specific mechanism of action of NCAPG in LUAD.

Results

Through comprehensive analysis of the GSE43458, GSE75037, and The Cancer Genome Atlas databases, we identified 517 overlapping DEGs. Among them, NCAPG was identified as a hub gene. Immunohistochemical analysis revealed that NCAPG was strongly associated with the clinical stage, M-classification, and N-classification. Univariate and multivariate Cox regression analyses indicated that NCAPG was a prognostic risk factor for LUAD, while the in vitro experiments showed that NCAPG overexpression promoted proliferation, migration, invasion, and epithelial-mesenchymal transition. Furthermore, knockdown of NCAPG inhibited LUAD progression, both in vitro and in vivo. Mechanistically, NCAPG overexpression increased p-Smad2 and p-Smad3 expressions in the transforming growth factor β (TGF-β) signaling pathway. Additionally, rescue experiments indicated that TGF-β signaling pathway inhibitors could restore the effect of NCAPG overexpression in LUAD cells.

Conclusions

NCAPG may promote proliferation and migration via the TGF-β signaling pathway in LUAD.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12935-021-02138-w.

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Most cited references 36

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Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

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Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.

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clusterProfiler: an R package for comparing biological themes among gene clusters.

Guangchuang Yu, Li-Gen Wang, Yanyan Han … (2012)

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Author and article information

Contributors

Hongru Li: muzi131122@163.com

Yusheng Chen:

ORCID: http://orcid.org/0000-0002-0048-0169

cysktz@fjmu.edu.cn

Journal

Journal ID (nlm-ta): Cancer Cell Int

Journal ID (iso-abbrev): Cancer Cell Int

Title: Cancer Cell International

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2867

Publication date (Electronic): 21 August 2021

Publication date PMC-release: 21 August 2021

Publication date Collection: 2021

Volume: 21

Electronic Location Identifier: 443

Affiliations

[1 ]GRID grid.256112.3, ISNI 0000 0004 1797 9307, Shengli Clinical Medical College of Fujian Medical University, ; Fuzhou, 350001 China

[2 ]GRID grid.415108.9, ISNI 0000 0004 1757 9178, Department of Pulmonary and Critical Care Medicine, , Fujian Provincial Hospital, ; Fuzhou, 350001 China

[3 ]Fujian Provincial Researching Laboratory of Respiratory Diseases, Fuzhou, 350001 China

Author information

Yusheng Chen http://orcid.org/0000-0002-0048-0169

Article

Publisher ID: 2138

DOI: 10.1186/s12935-021-02138-w

PMC ID: 8380402

PubMed ID: 34419073

SO-VID: 00c52282-b967-4e34-9a71-ec2fb90f1fd3

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 30 May 2021

Date accepted : 3 August 2021

Funding

Funded by: Natural Science Foundation of China

Award ID: 82002457

Award Recipient : Hongru Li

Funded by: Startup Fund for scientific research, Fujian Medical University

Award ID: 2019QH2045

Award ID: 2018QH1130

Award Recipient : Yun Wu Xunwei Tu

Funded by: Health research talents training program of Fujian province

Award ID: 2019-ZQNB-1

Award Recipient : Hongru Li

Funded by: high-level hospital grants from Fujian Provincial Hospital, Fujian province, China

Award ID: 2018GSP008

Award Recipient : Yusheng Chen

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: lung adenocarcinoma,ncapg,tgf-β signaling pathway,prognostic biomarkers

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: lung adenocarcinoma, ncapg, tgf-β signaling pathway, prognostic biomarkers

NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway

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Abstract

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Supplementary Information

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Karger: Oncology

Most cited references 36

Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

clusterProfiler: an R package for comparing biological themes among gene clusters.

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

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