MicroRNA-340-5p inhibits the malignant phenotypes of osteosarcoma by directly targeting NRF2 and deactivating the PI3K/AKT pathway

H.-P. Fan, S.-Y. Wang, Y.-Y. Shi, J. Sun

Department of Pediatrics, Yantai Maternity and Child Care Hospital, Yantaishan Hospital, Yantai, China. xiangkangbuxing540@163.com

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• Oncology

OBJECTIVE: The aim of the study was to examine the effects and potential mechanisms of miR-340-5p in Osteosarcoma (OS) progression.

PATIENTS AND METHODS: qRT-PCR was applied to detect expressions of miR-340-5p and NRF2 mRNA. MTT and transwell assay were carried out to determine the roles of miR-340-5p in OS cells viability, invasion and migration. TargetScan and Luciferase reporter assays were performed to search for the candidate target gene of miR-340-5p. The regulatory roles of miR-340-5p in OS PI3K/AKT pathway and EMT were examined by Western blot.

RESULTS: MiR-340-5p expressions were decreased in OS tissues and cells. Moreover, the decreased miR-340-5p expressions in OS tissues were frequently accompanied by shorter overall survival and malignant clinicopathologic features of OS patients. MTT assay showed that miR-340-5p upregulation prominently repressed OS cell proliferation. In addition, miR-340-5p restoration could significantly suppress OS cell invasion and migration as demonstrated by transwell assays. Results also revealed that miR-340-5p could directly target NRF2 and regulate PI3K/AKT pathway and EMT, exerting prohibitory functions in OS.

CONCLUSIONS: MiR-340-5p repressed the malignant phenotypes of OS via targeting NRF2 and regulating PI3K/AKT pathway and EMT. The current study provided preclinical evidence for the potential applications of miR-340-5p/NRF2 axis in OS therapies.

 

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