CircYAP1 inhibits osteosarcoma progression through the miR-135b-5p/FRK axis
Circular RNAs (circRNAs) are implicated in the progression of various malignancies, including osteosarcoma. However, little is known about the role of circYAP1 in osteosarcoma. In the present study, the expression of circYAP1 was found to be downregulated in osteosarcoma tissues relative to adjacent normal tissues. Decreased circYAP1 expression was also found in metastatic osteosarcoma specimens relative to nonmetastatic specimens, and low circYAP1 group had a higher metastasis rate and more advanced clinical stage than high circYAP1 group. <i>In vitro</i> functional assays demonstrated the inhibitory effects of circYAP1 on osteosarcoma cell proliferation, invasion, and migration. Regarding the mechanism, circYAP1 acts as a competitive endogenous RNA (ceRNA) to sponge miR-135b-5p, whereas FRK is a direct target of miR-135b-5p. Finally, a tumor-suppressing role of circYAP1 was demonstrated in the orthotopic lung metastasis models. In conclusion, our data reveal a tumor-suppressing role of circYAP1 and circYAP1/miR-135b-5p/FRK axis in osteosarcoma, demonstrating potential therapeutic targets for osteosarcoma.
Authors
- Qingqing Geng
- Qingxiang Zhang (ORCID: https://orcid.org/0000-0003-0294-7647)
- Le Shen (ORCID: https://orcid.org/0000-0002-2563-0012)
- Ming‐Rui Du
- Menglin Cong
- Xian-Jing Zhang
- Kang Han (ORCID: https://orcid.org/0000-0002-9940-7075)
- Mingfu Shang (ORCID: https://orcid.org/0000-0001-7982-777X)
- Chengkui Cai
- Zheng Zhang (ORCID: https://orcid.org/0000-0002-8060-8301)
- Shusen Tan
- Xiaohan Zhang (ORCID: https://orcid.org/0000-0003-4360-2995)
- Lanbo Yang
Institutions
- People's Liberation Army 401 Hospital (CN)
- Affiliated Hospital of Shaanxi University of Chinese Medicine (CN)
- Command Hospital Air Force (IN)
- Qilu Hospital of Shandong University (CN)
- Luoyang Orthopedic-Traumatological Hospital of Henan Province (CN)
- Shaanxi University of Chinese Medicine (CN)
Publication Details
- Journal
- iScience
- Published
- 2025-06-09
- DOI
- https://doi.org/10.1016/j.isci.2025.112858
- Primary Topic
- Circular RNAs in diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Shandong Province
- Medical and Health Science and Technology Development Project of Shandong Province
- China National Funds for Distinguished Young Scientists
- National Natural Science Foundation of China-Shandong Joint Fund for Marine Science Research Centers