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环状 RNA ROCK1，一种新型环状 RNA，通过改变 miR-532-5p/PTEN 轴抑制骨肉瘤增殖和迁移。

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

机构信息

Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, 310003, Hangzhou, China.

Fourth Department of Orthopedics, Central Hospital Affiliated to Shenyang Medical College, Shenyang, People's Republic of China.

出版信息

Exp Mol Med. 2022 Jul;54(7):1024-1037. doi: 10.1038/s12276-022-00806-z. Epub 2022 Jul 25.

DOI:10.1038/s12276-022-00806-z
PMID:35879346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9356001/
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.

摘要

作为儿童和青少年中最常见的骨肿瘤，骨肉瘤（OS）的发病机制和转移仍然很大程度上不清楚。在这里，我们研究了一种新型环状 RNA（circRNA）circROCK1-E3/E4 的表达和功能，它是由 Rho 相关卷曲螺旋蛋白激酶 1（ROCK1）的外显子 3 和 4 反向剪接而成的。我们发现，circROCK1-E3/E4 受 RNA 结合蛋白 quaking（QKI）的调控，在 OS 中下调，并与 OS 患者不良的临床特征相关。功能增殖和细胞迁移实验表明，circROCK1-E3/E4 作为 OS 细胞中的肿瘤抑制因子发挥作用。在机制上，circROCK1-E3/E4 通过 microRNA-532-5p（miR-532-5p）海绵作用上调磷酸酶和张力蛋白同源物（PTEN）来抑制增殖和迁移。在构建的裸鼠模型中，circROCK1-E3/E4 抑制了体内肿瘤的生长和肺转移。这项研究证明了 circROCK1-E3/E4 在 OS 进展中的功能和分子机制。这些发现可能为 OS 的分子治疗确定新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/ee8524181957/12276_2022_806_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/2f4250ecfda3/12276_2022_806_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/cc374bae3639/12276_2022_806_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/9d142af7ba56/12276_2022_806_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/044703b4a5b7/12276_2022_806_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/93855bb38217/12276_2022_806_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/ee8524181957/12276_2022_806_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/2f4250ecfda3/12276_2022_806_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/e0ac5a960e12/12276_2022_806_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/cc374bae3639/12276_2022_806_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/9d142af7ba56/12276_2022_806_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/044703b4a5b7/12276_2022_806_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/93855bb38217/12276_2022_806_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b2/9356001/ee8524181957/12276_2022_806_Fig7_HTML.jpg

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