miR-5195-3p Suppresses Cell Proliferation and Induces Apoptosis by Directly Targeting NEDD9 in Osteosarcoma
Luowen Wang1, Genbing Shi1, Donghui Zhu1
1Department of orthopedics, Shanghai Electric Power Hospital, Shanghai, China.
Abstract:
Aberrantly expressed microRNAs (miRs) have associated with the development and progression of osteosarcoma (OS). In this study, the authors aimed to investigate the biological function of miR-5195-3p and the underlying mechanisms. Quantitative real-time polymerase chain reaction analysis was performed to determine the expression of miR-5195-3p in OS tissues and cell lines. Then, two OS cell lines (MG-63 and U2OS) were transfected with miR-5195-3p mimics to obtain stably miR-5195-3p overexpression cell lines. A series of functional assays, including Cell Counting Kit-8 assay, colony formation assay, flow cytometry assay, and Hoechst staining were performed to analyze cell proliferation and apoptosis. The authors first observed downregulation of miR-5195-3p in OS tissues and cell lines. A series of functional assays demonstrated that miR-5195-3p overexpression significantly attenuated OS cell proliferative activity and induced apoptosis. At a molecular level, the neural precursor cell which expressed developmentally downregulated protein 9 (NEDD9), was inversely correlated with the expression level of miR-5195-3p. Furthermore, ectopic expression of NEDD9 counteracted the antiproliferative and apoptotic effects of miR-5195-3p overexpression in OS cells. In summary, the miR-5195-3p/NEDD9 axis may be a promising antitumor agent for OS.
Insights
MicroRNAs (miRs) like miR-5195-3p are crucial in osteosarcoma (OS) development. This study shows miR-5195-3p inhibits OS cell growth and promotes apoptosis by targeting NEDD9, suggesting a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant microRNA (miR) expression is linked to osteosarcoma (OS) development and progression.
- Understanding the specific roles of miRs in OS is critical for identifying novel therapeutic targets.
Purpose of the Study:
- To investigate the biological function of miR-5195-3p in osteosarcoma.
- To elucidate the molecular mechanisms underlying miR-5195-3p's role in OS.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to assess miR-5195-3p expression.
- Transfection of OS cell lines (MG-63, U2OS) with miR-5195-3p mimics.
- Functional assays including CCK-8, colony formation, flow cytometry, and Hoechst staining to evaluate cell proliferation and apoptosis.
- Analysis of neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) expression.
Main Results:
- miR-5195-3p was found to be downregulated in OS tissues and cell lines.
- Overexpression of miR-5195-3p significantly reduced OS cell proliferation and induced apoptosis.
- NEDD9 expression was inversely correlated with miR-5195-3p levels.
- Ectopic expression of NEDD9 reversed the anti-proliferative and pro-apoptotic effects of miR-5195-3p.
Conclusions:
- The miR-5195-3p/NEDD9 axis plays a significant role in regulating osteosarcoma cell behavior.
- miR-5195-3p acts as a tumor suppressor in osteosarcoma.
- The miR-5195-3p/NEDD9 pathway represents a potential therapeutic target for osteosarcoma treatment.
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