MicroRNA-584 Impairs Cellular Proliferation and Sensitizes Osteosarcoma Cells to Cisplatin and Taxanes by Targeting CCN2
Authors Li L, Kong X, Zang M, Hu B, Fang X, Gui B, Hu Y
Received 18 January 2020
Accepted for publication 31 March 2020
Published 15 April 2020 Volume 2020:12 Pages 2577—2587
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Kenan Onel
Li Li,1,2,* Xiang’an Kong,2,* Mousheng Zang,2 Bin Hu,2 Xing Fang,2 Binjie Gui,1 Yong Hu1
1Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Orthopedics, The Second People’s Hospital of Hefei, The Affiliated Hefei Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yong Hu Tel +86-551-62923605
Background: Osteosarcoma (OS), an aggressive malignant neoplasm, exhibits osteoblastic differentiation. Cisplatin (DDP) and taxanes are among the most effective drugs for OS patients. Nevertheless, the drug resistance remains a main limitation to efficacious chemotherapy in OS. The current report sets to explore the biological function of microRNA-584 (miR-584) and the potential mechanism underlying OS cells resistance to these two drugs.
Materials and Methods: The expression profiles of miR-584 and connective tissue growth factor (CTGF, CCN2) in OS tissue samples and cell lines were tested by means of reverse transcription-quantitative polymerase chain reaction and Western blot. U2OS and MG63 cell lines were delivered with miR-584 mimic alone or plus CCN2 to excavate theirs functions by cell counting kit-8 and EdU, flow cytometric analysis, as well as transwell assay, severally. Western bot analysis was conducted to examine the expression of IκBα, pIκBα, NF-κB and pNF-κB. Dual-luciferase reporter gene assay was carried out to assess the targets of miR-584.
Results: The downregulation of miR-584 was identified in OS tissues and cells, which was closely linked to the dismal prognosis of OS patients. Overexpression of miR-584 repressed cell viability, migration as well as invasion, potentiated apoptosis and sensitized OS cells to DDP and taxanes. Mechanism investigation specified a direct targeting relationship between CCN2 and miR-584 in OS.
Conclusion: In conclusion, miR-584 has the potency to act as a therapeutic maneuver for OS mainly by inducing the chemosensitivity of OS cells to DDP and taxanes.
Keywords: osteosarcoma, microRNA-584, CCN2, the IκBα/NF-κB signaling pathway, chemoresistance
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]