MiR‐421 promotes apoptosis and suppresses metastasis of osteosarcoma cells via targeting LTBP2. Issue 7 (28th March 2019)

• Record Type: Journal Article
• Authors: Liang, Xiaoju; Zhang, Lijun; Ji, Qiang; Wang, Bing; Wei, Dengke; Cheng, Deliang
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 7(2019)
• Page Start: 10978
• Page End: 10987
• Publication Date: 2019-03-28
• Subjects: apoptosis -- epithelial‐mesenchymal transition -- latent transforming growth factor β‐binding protein 2 -- miR‐421 -- osteosarcoma; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28144
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Increasing evidence has confirmed that microRNAs (miRs) are involved in tumor development and progression. A previous study reported that miR‐421 could serve as a diagnostic marker in patients with osteosarcoma (OS). The present study explored the potential roles of miR‐421 in the regulation of cell proliferation, apoptosis, migration, invasion, and epithelial‐mesenchymal transition of OS cells. Our results showed that miR‐421 was upregulated in OS tissues and cell lines (MG63, U2OS, HOS, and Saos‐2) compared with the corresponding adjacent tissues or human osteoblast cells hFOB1.19, while the latent transforming growth factor β‐binding protein 2 (LTBP2) expression was reduced. In MG63 and U2OS cells, CCK8 assay displayed that cell proliferation was repressed by the miR‐421 inhibitor, conversely increased by miR‐421 mimics. Inhibition of miR‐421 promoted cell apoptosis rate, caspase 3 activity, cleaved‐caspase 3 (c‐caspase 3) expression, and Bax/Bcl‐2 ratio, restoration of miR‐421 showed the opposite functions. Suppression of miR‐421 blocked migration and invasion, whereas miR‐421 overexpression promoted the migration and invasion of MG63 and U2OS cells. In addition, real‐time polymerase chain reaction and Western blot analysis revealed that miR‐421 negatively regulated E‐cadherin expression, and positively regulated the expression of N‐cadherin and vimentin. The luciferase reporter assay determined that miR‐421 could target LTBP2‐3′‐UTR, and LTBP2 expression was regulated negatively by miR‐421 both in mRNA and protein levels. Depletion of LTBP2 partly abolished the biological functions of miR‐421 inhibitor in OS. In conclusion, miR‐421 plays an oncogenic role in OS via targeting LTBP2, suggesting that miR‐421 may be a potential therapeutic target against OS. Abstract : Th knockdown of miR‐421 significantly increased cell apoptosis and suppressed epithelial‐mesenchymal transition in MG63 and U2OS cells, while forcing the expression of miR‐421 caused inverse roles. In addition, miR‐421 could target the latent transforming growth factor β‐binding protein 2 (LTBP2) 3′‐UTR, and silencing LTBP2 abrogated the biological activities of miR‐421 in osteosarcoma.