Effect of CUL4A on the metastatic potential of lung adenocarcinoma to the bone

Cao,Pei‑Pei; Chen,Wen‑Juan; Pang,Hai‑Lin; Shen,Wei‑Wei; Xue,Peng; Duan,Lian; Xu,Yu‑Xuan; Liu,Li‑Li; Zhang,He‑Long

doi:10.3892/or.2019.7448

Effect of CUL4A on the metastatic potential of lung adenocarcinoma to the bone

Authors:
- Pei‑Pei Cao
- Wen‑Juan Chen
- Hai‑Lin Pang
- Wei‑Wei Shen
- Peng Xue
- Lian Duan
- Yu‑Xuan Xu
- Li‑Li Liu
- He‑Long Zhang
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Affiliations: Department of Oncology, Tangdu Hospital, The Air Force Medical University, Xi'an, Shaanxi 710038, P.R. China, Department of Oncology, Tumor Hospital of Shaanxi Province, Xi'an, Shaanxi 710061, P.R. China, Department of Orthopedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China
Published online on: December 27, 2019 https://doi.org/10.3892/or.2019.7448
Pages: 662-670

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Abstract

Cullin 4A (CUL4A) is a member of the cullin family of proteins and has been demonstrated to be abnormally expressed in various types of malignancies. However, the function of CUL4A in metastasis of lung adenocarcinoma to the bone has rarely been reported. The aim of present of the study was to explore the biological functions and potential underlying molecular mechanisms of CUL4A in lung adenocarcinoma, highlighting a novel therapeutic target for the diagnosis and treatment of patients with lung adenocarcinoma. A549‑CUL4A, H1299‑CUL4A and H460‑shCUL4A cells were created using lentiviral infection. The efficiency of knockdown or overexpression was assessed using reverse transcription‑quantitative PCR and western blotting. The effects of CUL4A on proliferation, migration and invasion of lung adenocarcinoma cells in vitro and metastasis to the bone in vivo were determined using an MTT assay, colony formation assay, wound‑healing assay, Transwell assay and a mouse model of bone metastasis. The relationship between CUL4A and the EMT‑activator zinc finger E‑box binding homeobox 1 (ZEB1) were detected by western blotting. The results showed that overexpression of CUL4A in lung adenocarcinoma cells increased proliferation, migration and invasion, and increased metastasis of A549 to the bones in vivo. Silencing of CUL4A expression in lung adenocarcinoma cells reduced proliferation, migration and invasion in vitro. Mechanistically, CUL4A transcriptionally upregulated expression of ZEB1 which resulted in epithelial‑mesenchymal transition, which in turn promoted metastasis of lung adenocarcinoma to the bones. Taken together, these results suggest that CUL4A may serve an important regulatory role in the development of metastasis of lung adenocarcinoma to the bone.

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