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Updated: Dec 21, 2025

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1
Shu-Tao Zhu1, Xiao Wang1, Jun-Yi Wang1
1Department of Orthopedics, Huaihe Hospital, The First Affiliated Hospital of Henan University, Kaifeng, China.
Abstract:
The epithelial-mesenchymal transition (EMT) is a vital step in osteosarcoma (OS) progression toward metastasis, but the specific molecular events governing this process are incompletely characterized, with miRNAs having increasingly been found to regulate the EMT. In this study, We assessed levels of miR-22 and its target, Twist1, via real-time PCR (qRT-PCR). We further used functional proliferation assays, measures of cell morphology, and western blotting to assess the functional relevance of miR-22 in OS and confirmed Twist1 as a miR-22 target via luciferase reporter assay. We observed a significant decrease in miR-22 levels in OS tumor samples relative to normal tissue, with such downregulating being significantly associated with tumor histological grade. When overexpressed, miR-22 impaired OS cell proliferation and EMT progression. We found Twist1 to be a direct miR-22 target, with levels of miR-22 and Twist1 mRNA being inversely correlated in patient samples. When overexpressed, miR-22 suppressed Twist1 translation and thereby attenuated the EMT in OS cells. These results clearly demonstrate that miR-22 can regulate the EMT in OS cells via targeting Twist1, thus highlighting a potentially novel pathway that can be therapeutically targeted in order to treat OS.
Insights
MicroRNA-22 (miR-22) suppresses osteosarcoma (OS) progression by targeting Twist1, a key regulator of metastasis. Lower miR-22 levels correlate with higher tumor grade, suggesting miR-22 as a potential therapeutic target for OS.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- The epithelial-mesenchymal transition (EMT) is crucial for osteosarcoma (OS) metastasis.
- The molecular mechanisms regulating EMT in OS are not fully understood.
- MicroRNAs (miRNAs) are increasingly recognized as regulators of EMT.
Purpose of the Study:
- To investigate the role of miR-22 in regulating EMT in OS.
- To identify and validate the target of miR-22 involved in OS progression.
- To explore the therapeutic potential of targeting the miR-22/Twist1 pathway in OS.
Main Methods:
- Real-time PCR (qRT-PCR) to quantify miR-22 and Twist1 mRNA levels.
- Functional assays (proliferation, cell morphology) and Western blotting to assess miR-22 function.
- Luciferase reporter assay to confirm Twist1 as a direct miR-22 target.
Main Results:
- miR-22 levels were significantly decreased in OS tumors compared to normal tissue.
- Downregulation of miR-22 was associated with higher tumor histological grade.
- Overexpression of miR-22 inhibited OS cell proliferation and EMT.
- Twist1 was confirmed as a direct target of miR-22, with inverse correlation in patient samples.
- miR-22 suppressed Twist1 translation, attenuating EMT in OS cells.
Conclusions:
- miR-22 directly targets Twist1 to regulate EMT in osteosarcoma.
- The miR-22/Twist1 axis represents a potential therapeutic target for OS treatment.
- Restoring miR-22 levels may offer a novel strategy to combat OS metastasis.
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