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miR-141-3p is a key negative regulator of the EGFR pathway in osteosarcoma

Authors Wang J, Wang G, Li B, Qiu C, He M

Received 16 April 2018

Accepted for publication 29 June 2018

Published 31 July 2018 Volume 2018:11 Pages 4461—4478

DOI https://doi.org/10.2147/OTT.S171304

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Takuya Aoki


Jiashi Wang, Guangbin Wang, Bin Li, Chuang Qiu, Ming He

Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China

Background: Many studies have used miRNA to modulate osteosarcoma development by regulating protein expression, and these studies showed that the expression of EGFR is increased in osteosarcoma.
Methods: Western blot, real-time PCR and immunohistochemical were used to detect the expression of EGFR and miR-141 in osteosarcoma tissues and cells. The correlation between miR-141 and the grading of osteosarcoma and the correlation with the survival time of the patients were analyzed. After predicting the target effect of miR-141 on EGFR by miRDB, correlation analysis was used to analyze the correlation between miR-141 and EGFR. Luciferase reporter gene, western blot and real-time PCR were used to detect the targeting effect of miR-141 on EGFR. Then we detected the effect of miR-141 on proliferation by MTT and PI staining. The effect of miR-141 on cell apoptosis was detected by Hochest33258 and AV-PI staining, and the effect of miR-141 on cell migration was detected by Transwell. The regulatory effects of miR-141 on related proteins were detected by western blot and real-time PCR. Finally, we transfected EGFR and EGFR DEL (mutation with miR-141 binding site) in osteosarcoma cells, and detected the effects of miR-141 on cell proliferation, apoptosis, migration and related proteins.
Results: The expression of miR-141-3p was negatively correlated with the expression of EGFR in osteosarcoma. The overexpression of miR-141-3p was not only closely related to the classification and size of the osteosarcoma but also had a negative effect on the growth and migration of the osteosarcoma through negative regulation of the expression of EGFR. MiR-141 can inhibit the growth and metastasis of osteosarcoma cells by targeting EGFR and affecting its downstream pathway proteins.
Conclusion: Our study provides miR-141-3p may be a new theoretical basis for the treatment of osteosarcoma.

Keywords: EGFR, osteosarcoma, prognosis, growth, migration

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