Circular RNA ROCK1, a novel circRNA, suppresses osteosarcoma proliferation and migration via altering the miR-532-5p/PTEN axis
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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
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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