CircYAP1 inhibits osteosarcoma progression through the miR-135b-5p/FRK axis

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-09 DOI:10.1016/j.isci.2025.112858

Mingrui Du , Xuesan Zhang , Menglin Cong , Chengkui Cai , Qingxiang Zhang , Haixia Xin , Lanbo Yang , Qingqing Geng , Mingfu Shang , Zheng Zhang , Le Shen , Shusen Tan , Kang Han

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Abstract

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. In vitro 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.

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CircYAP1通过miR-135b-5p/FRK轴抑制骨肉瘤进展

环状rna （circRNAs）与包括骨肉瘤在内的各种恶性肿瘤的进展有关。然而，circYAP1在骨肉瘤中的作用知之甚少。在本研究中，我们发现circYAP1在骨肉瘤组织中相对于邻近的正常组织表达下调。与非转移性骨肉瘤标本相比，转移性骨肉瘤标本中circYAP1的表达也有所降低，且circYAP1低表达组的转移率高于高表达组，且circYAP1高表达组的临床分期更晚。体外功能实验证明circYAP1对骨肉瘤细胞增殖、侵袭和迁移具有抑制作用。关于其机制，circYAP1作为竞争性内源性RNA （ceRNA）海绵miR-135b-5p，而FRK是miR-135b-5p的直接靶点。最后，在原位肺转移模型中证实了circYAP1的肿瘤抑制作用。总之，我们的数据揭示了circYAP1和circYAP1/miR-135b-5p/FRK轴在骨肉瘤中的肿瘤抑制作用，证明了骨肉瘤的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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