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.
Background
Long non-coding RNAs (lncRNAs) have been implicated in initiation and development of numerous cancers. In the present study, we explored the role of lncRNAs AC007207.2 in osteosarcoma (OS).
Methods
Gene expression data of OS tissues was downloaded from the TARGET database. All the experiments were repeated at least three times. Data were analyzed using Perl, R, SPSS v12.0 and GraphPad Prism 8 software.
Results
We found lncRNA AC007207.2 was over-expressed in OS tissues and cell lines, and this phenomenon was associated with the worse prognosis of OS. Moreover, we found that AC007207.2 promotes proliferation and metastasis of OS cells via the miR-1306-5p/SIRT7 axis. Meanwhile, we found miR-1306-5p remarkably inhibits the malignant behavior of OS cells.
Conclusion
lncRNA AC007207.2 promotes progression of OS by upregulating SIRT7 expression through miR-1306-5p sponging. Thus, lncRNA AC007207.2/miR-1306-5p/SIRT7 axis is a promising therapeutic target for OS treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.