Upregulated osteoprotegerin expression promotes lung cancer cell invasion by increasing miR‑20a expression

Wan,Ke; Tu,Ziwei; Liu,Zhentian; Cai,Yun; Chen,Yinglan; Ling,Chunhua

doi:10.3892/etm.2021.10278

Upregulated osteoprotegerin expression promotes lung cancer cell invasion by increasing miR‑20a expression

Authors:
- Ke Wan
- Ziwei Tu
- Zhentian Liu
- Yun Cai
- Yinglan Chen
- Chunhua Ling
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Affiliations: Department of Respiratory Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China, Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China, Department of Thoracic Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
Published online on: June 7, 2021 https://doi.org/10.3892/etm.2021.10278
Article Number: 846
Copyright: © Wan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and a major regulatory factor in osteoclast development. OPG has been previously associated with the malignant behavior of various types of cancer, particularly that of cancer metastasis. However, information on the link between the expression profile of OPG and lung cancer metastasis remained elusive. In the present study, the expression levels of OPG in the serum samples of patients with non‑small cell lung cancer (NSCLC) was measured using ELISA. The expression of miRNAs was assessed using reverse transcription‑quantitative PCR. A549 or H3122 cell invasion was assessed using Transwell invasion assays. The effect of OPG on the invasiveness of lung cancer cells was evaluated using an experimental mouse lung metastasis model. OPG expression was found to be upregulated in the serum of patients with NSCLC compared with that in healthy individuals. The serum levels of OPG in patients with distant metastasis were observably higher compared with those in patients without metastasis. Functionally, overexpression of OPG in NSCLC cells markedly promoted cell invasion. Mechanistically, increased expression of OPG resulted in upregulation of microRNA (miR)‑20a in NSCLC cells. Furthermore, miR‑20a promoted NSCLC cell invasion, whilst miR‑20a inhibition partially abrogated the effect of OPG on NSCLC cell invasion. Taken together, the present results demonstrated that the OPG/miR‑20a axis serve an important role in lung cancer metastasis, which potentially provide an additional novel target for lung cancer treatment.

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