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MicroRNA-876-5p inhibits cell proliferation, migration and invasion by targeting c-Met in osteosarcoma
Weixin Xie1, Jie Xiao2, Tao Wang3
1Department of Orthopaedic Surgery, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
Abstract:
Recently, aberrant expression of miR-876-5p has been reported to participate in the progression of several human cancers. However, the expression and function of miR-876-5p in osteosarcoma (OS) are still unknown. Here, we found that the expression of miR-876-5p was significantly down-regulated in OS tissues compared to para-cancerous tissues. Clinical association analysis indicated that underexpression of miR-876-5p was positively correlated with advanced clinical stage and poor differentiation. More importantly, OS patients with low miR-876-5p level had a significant shorter overall survival compared to miR-876-5p high-expressing patients. In addition, gain- and loss-of-function experiments demonstrated that miR-876-5p restoration suppressed whereas miR-876-5p knockdown promoted cell proliferation, migration and invasion in both U2OS and MG63 cells. In vivo studies revealed that miR-876-5p overexpression inhibited tumour growth of OS in mice. Mechanistically, miR-876-5p reduced c-Met abundance in OS cells and inversely correlated c-Met expression in OS tissues. Herein, c-Met was recognized as a direct target of miR-876-5p using luciferase reporter assay. Notably, c-Met restoration rescued miR-876-5p attenuated the proliferation, migration and invasion of OS cells. In conclusion, these findings indicate that miR-876-5p may be used as a potential therapeutic target and promising biomarker for the diagnosis and prognosis of OS.
Insights
MicroRNA-876-5p (miR-876-5p) is down-regulated in osteosarcoma (OS), suppressing tumor growth and progression. Low miR-876-5p levels correlate with poor prognosis, suggesting its potential as a diagnostic and therapeutic target for OS.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Aberrant microRNA (miRNA) expression is implicated in human cancer progression.
- The role of miR-876-5p in osteosarcoma (OS) remains uncharacterized.
Purpose of the Study:
- To investigate the expression, function, and clinical significance of miR-876-5p in osteosarcoma.
- To elucidate the underlying molecular mechanisms of miR-876-5p in OS progression.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for miR-876-5p expression analysis in OS tissues and cell lines.
- Gain- and loss-of-function assays (transfection with miR-876-5p mimics and inhibitors) to assess cellular proliferation, migration, and invasion.
- In vivo tumor xenograft models in mice to evaluate the effect of miR-876-5p overexpression on tumor growth.
- Luciferase reporter assays to confirm c-Met as a direct target of miR-876-5p.
Main Results:
- miR-876-5p expression was significantly downregulated in OS tissues compared to adjacent normal tissues.
- Downregulation of miR-876-5p correlated with advanced clinical stage, poor differentiation, and shorter overall survival in OS patients.
- Restoration of miR-876-5p suppressed OS cell proliferation, migration, and invasion, while knockdown promoted these processes.
- Overexpression of miR-876-5p inhibited OS tumor growth in vivo.
- miR-876-5p directly targeted c-Met, reducing its expression in OS cells and tissues.
- Restoration of c-Met expression rescued the inhibitory effects of miR-876-5p on OS cell behaviors.
Conclusions:
- miR-876-5p functions as a tumor suppressor in osteosarcoma.
- miR-876-5p inhibits OS cell proliferation, migration, and invasion by targeting c-Met.
- miR-876-5p may serve as a potential therapeutic target and prognostic biomarker for osteosarcoma.
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