Dataset Information

Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/?-catenin pathway.

ABSTRACT: Chromobox 4 (CBX4) is a core component of polycomb-repressive complex 1 with important roles in cancer biology and tissue homeostasis. Aberrant expression of CBX4 has been implicated in several human malignancies. However, its role and underlying mechanisms in the tumorigenesis of lung adenocarcinoma (LUAD) have not been defined in vivo. Here, we found that expression of CBX4 was frequently up-regulated in human LUAD samples and correlated with poor patient survival. Importantly, genetic ablation of CBX4 greatly dampened lung tumor formation and improved survival in the Kras^G12D/P53^L/L (KP) autochthonous mouse model of LUAD. In addition, CBX4 depletion significantly inhibited proliferation and anchorage-independent growth of KP mouse embryonic fibroblasts. Moreover, ectopic CBX4 expression clearly promoted proliferation and anchorage-independent growth in both human and mouse LUAD cells, whereas silencing of CBX4 exerted opposite effects. Mechanistically, CBX4 promoted growth of LUAD cells through activation of the Wnt/?-catenin pathway. Furthermore, expression levels of CBX4 were positively correlated with ?-catenin in human LUAD samples. In conclusion, our data suggest that CBX4 plays an oncogenic role via the Wnt/?-catenin pathway and could serve as a potential therapeutic target in LUAD.

SUBMITTER: Wang Z

PROVIDER: S-EPMC7797484 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/β-catenin pathway.

Wang Zuoyun Z Fang Zhaoyuan Z Chen Gaobin G Liu Bo B Xu Jinjin J Li Fei F Li Fuming F Liu Hongyan H Zhang Haoen H Sun Yihua Y Tian Gang G Chen Haiquan H Xu Guoliang G Zhang Lei L Hu Liang L Ji Hongbin H

Neoplasia (New York, N.Y.) 20201230 2

Chromobox 4 (CBX4) is a core component of polycomb-repressive complex 1 with important roles in cancer biology and tissue homeostasis. Aberrant expression of CBX4 has been implicated in several human malignancies. However, its role and underlying mechanisms in the tumorigenesis of lung adenocarcinoma (LUAD) have not been defined in vivo. Here, we found that expression of CBX4 was frequently up-regulated in human LUAD samples and correlated with poor patient survival. Importantly, genetic ablatio ...[more]

PMID: 33387960

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Project description:Lung cancer is a malignant tumor responsible for the highest mortality rate in humans. The identification of novel functional genes is of great importance in the treatment of lung cancer. The reported roles of replication factor C subunit 3 (RFC3) in tumorigenesis are contradictory. The present study aimed to explore the role and mechanism of RFC3 in lung cancer cells. An immunohistochemical study of 165 lung cancer and adjacent tissues was conducted (123 lung adenocarcinoma tissues and 42 lung squamous cell carcinoma tissues). Kaplan‑Meier analysis and Cox multivariate analysis were employed to explore the relationship between RFC3 and patient prognosis. In addition, the proliferation, cell cycle distribution and apoptosis of A549 and H1299 cells were determined by MTT assay and flow cytometry, respectively, following cell transfection to induce overexpression and knockdown of RFC3. A Boyden chamber assay and wound‑healing assay were conducted to determine the invasive and migratory abilities of A549 and H1299 cells. Western blotting was used to analyze the effects of RFC3 overexpression and RFC3 small interfering RNA‑induced knockdown, and to explore the potential mechanism and pathway underlying the effects of RFC3. Positive expression of RFC3 was detected in lung adenocarcinoma, and overexpression of RFC3 shortened the survival time of patients with lung adenocarcinoma. Furthermore, overexpression of RFC3 increased the invasion and migration of A549 cells, whereas knockdown of RFC3 significantly reduced the invasion and migration of H1299 cells. Ectopic expression of RFC3 induced epithelial‑mesenchymal transition (EMT), as determined by downregulation of E‑cadherin, and upregulation of N‑cadherin, vimentin and Wnt signaling target genes, including c‑MYC, Wnt1 and β‑catenin, and the ratio of phosphorylated‑glycogen synthase kinase 3 (GSK3)‑β (Ser9)/GSK3‑β. In conclusion, RFC3 may be considered a coactivator that promotes the Wnt/β‑catenin signaling pathway, and induces EMT and metastasis in lung adenocarcinoma.

Dataset Information

Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/?-catenin pathway.

Publications

Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/β-catenin pathway.

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