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Updated: Mar 29, 2026

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
miR-874 suppresses the proliferation and metastasis of osteosarcoma by targeting E2F3
Dong Dong1, Yubao Gong2, Debao Zhang2
1Department of Radiology, The First Hospital of Jilin University, No.71 Xinmin Street, Changchun, 130021, Jilin, China.
Abstract:
Increasing evidence indicates that microRNAs (miRNAs) play critical roles in osteosarcoma (OS) occurrence and development. MicroRNA-874 (miR-874) has proven to be dysregulated in several human cancers. However, the biological function and underlying molecular mechanism of miR-874 in OS remain unclear. In this study, we aimed to investigate the biological role and potential mechanism of miR-874 in OS. Here, we found that miR-874 expression was significantly decreased in OS cell lines and tissues by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and its expression was correlated with tumor-node-metastasis (TNM) stage, tumor size, and lymph node metastasis (all P < 0.01). Functional study revealed that overexpression of miR-874 in OS cells could remarkably inhibit proliferation, migration, and invasion and induce cell apoptosis. In addition, E2F transcription factor 3 (E2F3) was confirmed as a target of miR-874 in OS cells. E2F3 mRNA expression was upregulated and was inversely correlated with the level of miR-874 in OS tissues. Importantly, downregulation of E2F3 mimicked the effect of overexpression miR-874 in OS cells, and E2F3 overexpression partially attenuated the tumor-suppressive effects of miR-874 in OS cells. Taken together, these findings suggested that miR-874 might suppress the growth and metastasis of OS cells partially by targeting E2F3.
Insights
MicroRNA-874 (miR-874) is downregulated in osteosarcoma (OS). Restoring miR-874 inhibits OS cell proliferation and metastasis by targeting E2F transcription factor 3 (E2F3).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial in cancer development.
- MicroRNA-874 (miR-874) is dysregulated in various cancers, but its role in osteosarcoma (OS) is unknown.
Purpose of the Study:
- To investigate the function and mechanism of miR-874 in osteosarcoma.
- To determine if miR-874 acts as a tumor suppressor in OS.
Main Methods:
- Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess miR-874 expression.
- In vitro functional assays (proliferation, migration, invasion, apoptosis) in OS cells.
- Western blot and luciferase assays to confirm E2F3 as a target of miR-874.
Main Results:
- miR-874 expression was significantly decreased in OS tissues and cell lines.
- miR-874 expression inversely correlated with tumor stage, size, and metastasis.
- Overexpression of miR-874 inhibited OS cell proliferation, migration, and invasion, while promoting apoptosis.
- E2F transcription factor 3 (E2F3) was identified as a direct target of miR-874.
- Downregulation of E2F3 mimicked miR-874's tumor-suppressive effects; E2F3 overexpression partially reversed these effects.
Conclusions:
- miR-874 functions as a tumor suppressor in osteosarcoma.
- miR-874 inhibits OS cell growth and metastasis by targeting E2F3.
- miR-874 represents a potential therapeutic target for osteosarcoma treatment.
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