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Hypoxic Non-Small-Cell Lung Cancer Cell-Secreted Exosomal microRNA-582-3p Drives Cancer Cell Malignant Phenotypes by Targeting Secreted Frizzled-Related Protein 1

Authors Wang J, Zhao J, Zhu J, Zhang S

Received 20 May 2020

Accepted for publication 26 August 2020

Published 14 October 2020 Volume 2020:12 Pages 10151—10161

DOI https://doi.org/10.2147/CMAR.S263768

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly


Jian Wang,1 Jia Zhao,2 Jinsong Zhu,1 Shengli Zhang1

1Department of Respiration, People’s Hospital of Cangzhou, Cangzhou, Hebei, People’s Republic of China; 2Department of Neonatology, People’s Hospital of Cangzhou, Cangzhou, Hebei, People’s Republic of China

Correspondence: Jian Wang
Department of Respiratory, People’s Hospital of Cangzhou, 7 Qingchi Avenue, Cangzhou 061000, Hebei, People’s Republic of China
Email jianw205@126.com

Background: Hypoxic environment and exosomes (exos)-mediated intercellular communication are crucial for cancer invasion and metastasis, but the mechanisms are not yet fully understood. In this study, we investigated the regulatory effect of hypoxic tumor cell-secreted exosomal miR-582-3p on non-small-cell lung cancer (NSCLC) cell malignant phenotypes.
Methods: The concentration and diameters of exos were evaluated by nanosight particle tracking analysis. microRNA-582-3p (miR-582-3p) expression was detected by quantitative real-time PCR. The fluorescent dye PKH26 was used to label exos. The direct interaction between miR-582-3p and secreted frizzled-related protein 1 (SFRP1) was determined by dual-luciferase activity assay. NSCLC cell proliferation, migration, and invasion abilities were assessed by cell count kit-8 assay, wound healing assay, and transwell migration and invasion assay. Western blot analysis was performed to detect the protein expression level.
Results: Hypoxic NSCLC cell-derived exos promoted the proliferation, migration, and invasion of normoxic NSCLC cells. miR-582-3p expression was upregulated in hypoxic NSCLC cells and hypoxic NSCLC cell-secreted exos. Hypoxic NSCLC cell-derived exos transmitted miR-582-3p to normoxic NSCLC cells. Hypoxic NSCLC cell-secreted exosomal miR-582-3p promoted the proliferation, migration, and invasion of normoxic NSCLC cells. miR-582-3p inhibited the expression of SFRP1 protein by binding to its 3ʹ-UTR. In addition, enforced expression of SFRP1 restrained malignant phenotypes of normoxic NSCLC cells, which was abrogated by hypoxic NSCLC cell-secreted exosomal miR-582-3p.
Conclusion: Hypoxic NSCLC cell-secreted exosomal miR-582-3p drives cancer cell malignant phenotypes by targeting SFRP1, which provides a better understanding of cancer metastasis and may facilitate the development of therapeutics against human NSCLC.

Keywords: hypoxia, non-small-cell lung cancer, exosome, microRNA-582-3p, secreted frizzled‑related protein 1

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