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Updated: Sep 3, 2025

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Circular RNA ROCK1, a novel circRNA, suppresses osteosarcoma proliferation and migration via altering the
Yize Liu1,2, Guanzhen Qiu2, Yinzhou Luo2
1Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, 310003, Hangzhou, China.
Abstract:
As the most prevalent bone tumor in children and adolescents, the pathogenesis and metastasis of osteosarcoma (OS) remain largely unclear. Here, we investigated the expression and function of a novel circular RNA (circRNA), circROCK1-E3/E4, which is back-spliced from exons 3 and 4 of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) in OS. We found that circROCK1-E3/E4, regulated by the well-known RNA-binding protein quaking (QKI), was downregulated in OS and correlated with unfavorable clinical features of patients with OS. Functional proliferation and cell motility assays indicated that circROCK1-E3/E4 serves as a tumor suppressor in OS cells. Mechanistically, circROCK1-E3/E4 suppressed proliferation and migration by upregulating phosphatase and tensin homolog (PTEN) through microRNA-532-5p (miR-532-5p) sponging. In the constructed nude mouse model, circROCK1-E3/E4 inhibited tumor growth and lung metastasis in vivo. This study demonstrates the functions and molecular mechanisms of circROCK1-E3/E4 in the progression of OS. These findings may identify novel targets for the molecular therapy of OS.
Insights
A novel circular RNA, circROCK1-E3/E4, acts as a tumor suppressor in osteosarcoma (OS). It inhibits OS cell proliferation and metastasis by regulating PTEN, offering potential new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is the most common bone tumor in children and adolescents.
- The underlying mechanisms of OS pathogenesis and metastasis are not fully understood.
Purpose of the Study:
- To investigate the role and mechanism of a novel circular RNA, circROCK1-E3/E4, in osteosarcoma progression.
Main Methods:
- Investigated circROCK1-E3/E4 expression in OS tissues and cell lines.
- Performed functional assays (proliferation, cell motility) in OS cells.
- Utilized nude mouse models to assess in vivo tumor growth and metastasis.
- Conducted mechanistic studies involving microRNA-532-5p (miR-532-5p) and phosphatase and tensin homolog (PTEN).
Main Results:
- circROCK1-E3/E4 was downregulated in OS and associated with poor clinical outcomes.
- circROCK1-E3/E4 suppressed OS cell proliferation and migration.
- circROCK1-E3/E4 acts as a tumor suppressor by sponging miR-532-5p, leading to PTEN upregulation.
- In vivo studies showed circROCK1-E3/E4 inhibited tumor growth and lung metastasis.
Conclusions:
- circROCK1-E3/E4 functions as a tumor suppressor in osteosarcoma.
- The circROCK1-E3/E4/miR-532-5p/PTEN axis is a key pathway in OS progression.
- circROCK1-E3/E4 represents a potential therapeutic target for osteosarcoma.
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