RFC3 induces epithelial‑mesenchymal transition in lung adenocarcinoma cells through the Wnt/β‑catenin pathway and possesses prognostic value in lung adenocarcinoma

Gong,Shulei; Qu,Xiaohan; Yang,Shize; Zhou,Siyu; Li,Peiwen; Zhang,Qigang

doi:10.3892/ijmm.2019.4386

RFC3 induces epithelial‑mesenchymal transition in lung adenocarcinoma cells through the Wnt/β‑catenin pathway and possesses prognostic value in lung adenocarcinoma

Authors:
- Shulei Gong
- Xiaohan Qu
- Shize Yang
- Siyu Zhou
- Peiwen Li
- Qigang Zhang
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Affiliations: Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: October 29, 2019 https://doi.org/10.3892/ijmm.2019.4386
Pages: 2276-2288
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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