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

Yize Liu,Guanzhen Qiu,Yinzhou Luo,Shan-shan Li,Yeqiu Xu,Yuanzhuang Zhang,Jiayuan Hu,Peifeng Li,Hailing Pan,Yong Wang

Published 2022 in Experimental and Molecular Medicine

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. Understanding the role of a circular RNA molecule in bone cancer may provide a foundation for potential therapies. The factors underlying the development and progression of osteosarcoma, an aggressive bone cancer most common in young people, remain unclear. Circular RNAs (circRNAs), derived from RNA splicing events, have multiple functions in diseases such as cancer. Yong Wang at Zhejiang University, China, and co-workers had already demonstrated that the ROCK1 gene plays critical roles in osteosarcoma progression. Now, they have identified a novel circRNA called circROCK1-E3/E4 derived from ROCK1, which acts as a tumor suppressor in osteosarcoma. In experiments on human cell lines and mouse models, they found that circROCK1-E3/E4 regulates a key pathway that suppresses the proliferation and migration of cancer cells. Poor prognosis is linked to downregulated levels of this circRNA.

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