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敲低特异性环状非编码RNA显著抑制骨肉瘤的进展

Knockdown of a Specific Circular Non-Coding RNA Significantly Suppresses Osteosarcoma Progression
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摘要 骨肉瘤是一种间充质组织来源的恶性肿瘤,好发于儿童和青少年,发生肺转移常导致患者死亡。关于骨肉瘤进展的机制仍不清楚。因此,迫切需要开发新的骨肉瘤治疗靶点和治疗模式。异常表达的非编码环状RNA(circRNA)对骨肉瘤的发生和发展至关重要。本研究的目的是探索一种新的circRNA circ_000203在骨肉瘤中的表达和作用,阐明其潜在机制。我们发现,在骨肉瘤细胞系和组织中circ_000203高表达,并且circ_000203敲低显著抑制了体外和体内的骨肉瘤进展。此外,我们发现circ_000203是miR-26b-5p的海绵,而miR-26b-5p是骨形态发生蛋白受体2(BMPR2)的上游调节因子。因此,BMPR2的过表达可以减轻对骨肉瘤进展的抑制作用。这表明,敲低circ_000203可通过miRNA介导的BMPR2下调抑制骨肉瘤的进展。我们的发现为理解骨肉瘤的发生和发展提供了重要的见解。 Osteosarcoma(OS)is a malignant mesenchymal tissue tumor known to occur in children and adolescents,and pulmonary metastasis often leads to death in these patients.The mechanism underlying OS progression remains unclear.Therefore,identifying new therapeutic targets and treatment modalities for OS is urgently needed.Abnormally expressed non-coding circular RNAs(circRNAs)are crucial for the occurrence and development of OS.The purpose of this study was to explore the expression and role of a novel circRNA circ_000203 in OS and elucidate the underlying mechanism.circ_000203 was demonstrated highly expressed in OS cell lines and tissues,and circ_000203 knockdown significantly inhibited OS progression in vitro and in vivo.Furthermore,we found that circ_000203 is a sponge of miR-26b-5p,an upstream regulator of bone morphogenetic protein receptor 2(BMPR2).Thus,the overexpression of BMPR2 could reduce the inhibitory effect on OS progression.This indicates that knockdown of circ_000203 suppresses OS progression through microRNA(miRNA)-mediated BMPR2 downregulation.Our findings provide important insights for understanding the occurrence and development of OS.
作者 王世东 张红亮 李博 陈成龙 任婷婷 黄怡 刘凯 李敬敬 郭卫 Shidong Wang;Hongliang Zhang;Bo Li;Chenglong Chen;Tingting Ren;Yi Huang;Kai Liu;Jingjing Li;Wei Guo(Musculoskeletal Tumor Center,Peking University People’s Hospital,Beijing 100044,China;Beijing Key Laboratory of Musculoskeletal Tumor,Peking University People’s Hospital,Beijing 100044,China;Department of Spine Surgery and Musculoskeletal Tumor,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;State Key Laboratory of Rare Earth Resource Utilization,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China;Department of Chemistry,Tsinghua University,Beijing 100084,China)
出处 《Engineering》 SCIE EI CAS CSCD 2023年第2期188-194,M0007,共8页 工程(英文)
基金 supported by the Peking University People’s Hospital Research and Development Funds(RDY2018-13) the National Key Research and Development Program of China(2020YFA0908900) the National Natural Science Foundation of China(22107097) the Youth Innovation Promotion Association of Chinese Academy of Science(2021226)。
关键词 骨肉瘤 异常表达 间充质 肺转移 非编码RNA 儿童和青少年 敲低 恶性肿瘤 Non-coding RNA Osteosarcoma CircRNA Molecular mechanism Knockdown
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