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Updated: Jan 29, 2026

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Overexpression of miR-1258 inhibits cell proliferation by targeting AKT3 in osteosarcoma
Wei Liu1, Zhimin Zhou2, Qi Zhang3
1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; Department of Orthopaedics, West China Hospital Sichuan University, Chengdu, Sichuan, China.
Abstract:
Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumor which affects children and adolescents. A growing number of relevant studies have shown that many microRNAs (miRNAs) play a vital regulatory role in the etiology of various types of cancer. miR-1258 has been widely studied in various cancers, but there have been few studies of its role in OS. In this present study, miR-1258 expression was dramatically decreased in OS tissues as well as OS cell lines. In addition, decreased expression of miR-1258 was significantly associated with malignant clinical manifestations and poor clinical prognosis of patients with OS. Moreover, upregulation of miR-1258 significantly inhibited cell proliferation as well as promoting cell cycle arrest at G0/G1. AKT3 was identified as a direct target of miR-1258 by binding to its 3'-UTR, and miR-1258 was negatively correlated with AKT3 expression in clinical OS tissues. AKT3 was evidently upregulated in OS tissues and cells and upregulation of AKT3 accelerated the progression of OS. Moreover, through a series of rescue experiments, we demonstrated that AKT3 can abolish the role of miR-1258 in suppressing proliferation as well as regulating the cell cycle in OS cells. In conclusion, our results suggest that the miR-1258-AKT3 axis may be a promising prognostic marker and therapeutic target for human OS.
Insights
MicroRNA-1258 (miR-1258) is significantly decreased in osteosarcoma (OS), inhibiting cancer cell growth. Restoring miR-1258 shows potential for treating OS by targeting AKT3.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a primary bone cancer affecting children and adolescents.
- MicroRNAs (miRNAs) are crucial regulators in cancer development.
- The role of miR-1258 in OS remains understudied.
Purpose of the Study:
- To investigate the expression and function of miR-1258 in osteosarcoma.
- To identify the molecular targets and pathways regulated by miR-1258 in OS.
- To evaluate miR-1258 as a potential prognostic marker and therapeutic target for OS.
Main Methods:
- Quantitative real-time PCR to measure miR-1258 and AKT3 expression in OS tissues and cell lines.
- Cell proliferation assays and cell cycle analysis to assess the functional role of miR-1258.
- Bioinformatic analysis and luciferase reporter assays to identify AKT3 as a direct target of miR-1258.
- Rescue experiments to validate the miR-1258-AKT3 interaction in OS cells.
Main Results:
- miR-1258 expression was significantly downregulated in OS tissues and cell lines.
- Low miR-1258 expression correlated with advanced clinical manifestations and poor prognosis in OS patients.
- Upregulation of miR-1258 suppressed OS cell proliferation and induced G0/G1 cell cycle arrest.
- AKT3 was identified as a direct target of miR-1258, with its expression inversely correlated with miR-1258 in OS.
- AKT3 upregulation promoted OS progression, and its effects were rescued by inhibiting miR-1258.
Conclusions:
- The miR-1258-AKT3 axis plays a critical role in the development and progression of osteosarcoma.
- miR-1258 functions as a tumor suppressor in OS by targeting AKT3.
- The miR-1258-AKT3 pathway represents a potential prognostic biomarker and therapeutic target for osteosarcoma.
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