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Published on: May 3, 2021
miR-487a performs oncogenic functions in osteosarcoma by targeting BTG2 mRNA
Zhiqian Gu1,2, Shaokun Wu1,2, Guoxing Xu3
1Department of Orthopedics, Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No. 2 Hospital), Ningbo 315000, China.
Abstract:
Aberrant microRNA (miRNA) expression plays a critical role in osteosarcoma (OS) pathogenesis. In this study, we elucidated the involvement of miR-487a in OS and the underlying molecular mechanisms. We found that miR-487a was upregulated in OS clinical samples and cell lines. Knockdown of miR-487a suppressed OS cell growth and invasion and induced apoptosis; however, overexpression of miR-487a promoted OS cell growth and invasion. Accordingly, downregulation of miR-487a significantly suppressed tumor growth of OS xenografts in vivo. Furthermore, B-cell translocation gene 2 (BTG2) mRNA was found to be a novel target of miR-487a. Knockdown of BTG2 using small interfering RNA (siRNA) recapitulated the oncogenic effects of miR-487a, whereas BTG2 overexpression partially reversed these effects. Finally, miR-487a levels were found to be negatively correlated with BTG2 expression in OS clinical samples. Collectively, our data suggest that miR-487a is an oncogenic miRNA in OS and it lowers BTG2 expression.
Insights
MicroRNA-487a (miR-487a) is elevated in osteosarcoma, promoting tumor growth and invasion by downregulating B-cell translocation gene 2 (BTG2). Inhibiting miR-487a suppressed tumor progression in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant microRNA (miRNA) expression is implicated in osteosarcoma (OS) development.
- Understanding specific miRNA roles is crucial for OS pathogenesis research.
Purpose of the Study:
- To investigate the role of microRNA-487a (miR-487a) in osteosarcoma.
- To elucidate the molecular mechanisms by which miR-487a influences OS progression.
Main Methods:
- Analysis of miR-487a expression in OS clinical samples and cell lines.
- In vitro functional assays (cell growth, invasion, apoptosis) following miR-487a manipulation.
- In vivo studies using OS xenografts.
- Identification and validation of miR-487a targets using techniques like small interfering RNA (siRNA).
Main Results:
- miR-487a was significantly upregulated in OS tissues and cells.
- miR-487a knockdown inhibited OS cell proliferation, invasion, and tumor growth in vivo, while inducing apoptosis.
- miR-487a overexpression promoted OS cell growth and invasion.
- B-cell translocation gene 2 (BTG2) was identified as a direct target of miR-487a.
- BTG2 knockdown mimicked miR-487a's oncogenic effects, and BTG2 overexpression partially reversed them.
- A negative correlation between miR-487a and BTG2 expression was observed in OS samples.
Conclusions:
- miR-487a acts as an oncogenic miRNA in osteosarcoma.
- miR-487a promotes OS progression by suppressing the expression of its target gene, BTG2.
- Targeting miR-487a represents a potential therapeutic strategy for osteosarcoma.
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