circUSP34 accelerates osteosarcoma malignant progression by sponging miR-16-5p.
circUSP34 accelerates osteosarcoma malignant progression by sponging miR-16-5p.
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DOI：
10.1111/cas.15147
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发表时间：
2022-01
期刊：
影响因子：
5.7
通讯作者：
Guo W
中科院分区：
文献类型：
--
作者：
Lou J;Zhang H;Xu J;Ren T;Huang Y;Tang X;Guo W
骨肉瘤是一种原发性高度恶性的间叶组织肿瘤。疾病发生或进展的具体病理机制尚不清楚。环状RNA（CircRNA）是一类具有首尾连接位点的共价环状RNA。在本研究中，我们的目的是研究circRNA和microRNA（miRNAs）在OS中的海绵机制。基于miR-16 - 5 p对OS的抑制作用，通过Starbase分析circUSP 34作为miR-16 - 5 p的海绵。我们发现circUSP 34在体外和体内促进OS的增殖、迁移和侵袭。通过qRT-PCR，在OS中circUSP 34增加，但miR-16 - 5 p减少。功能分析表明，敲除circUSP 34后，OS细胞的恶性，包括增殖，迁移和侵袭，受到抑制。Western blotting结果显示vimentin和Ki-67的表达水平降低。类似地，miR-16 - 5 p模拟物损害OS细胞的增殖、迁移和侵袭。FISH检测结果表明，circUSP 34和miR-16 - 5 p共定位于细胞质中。通过双荧光素酶报告基因测定、RNA免疫沉淀（RIP）和RNA下拉测定验证了circUSP 34和miR-16 - 5 p的海绵机制。有趣的是，miR-16 - 5 p抑制剂部分逆转了sh-circUSP 34对OS细胞恶性肿瘤的抑制作用。此外，用于IHC的小鼠肿瘤表明波形蛋白、N-钙粘蛋白和Ki-67蛋白表达降低，但E-钙粘蛋白蛋白表达增加。总的来说，circUSP 34通过吸收miR-16 - 5 p促进OS恶性肿瘤，包括增殖、迁移和侵袭。它可以作为一个潜在的治疗靶点和生物标志物。本文对骨肉瘤的调控机制进行了深入的研究，为骨肉瘤的治疗提供了新的生物标志物和潜在的治疗靶点。
Osteosarcoma (OS) is a primary and highly malignant mesenchymal tissue tumor. The specific pathological mechanism underlying disease initiation or progression remains unclear. Circular RNAs (circRNAs) are a type of covalently circular RNA with a head‐to‐tail junction site. In this study, we aimed to investigate the sponging mechanism between circRNAs and microRNAs (miRNAs) in OS. Based on the inhibited effect of miR‐16‐5p reported on OS, circUSP34 was analyzed as a sponge of miR‐16‐5p via Starbase. We found that circUSP34 promoted the proliferation, migration, and invasion of OS in vitro and in vivo. circUSP34 increased but miR‐16‐5p decreased in OS by qRT‐PCR. Function assays showed that the malignancy of OS cells, including proliferation, migration, and invasion, was inhibited after knocking out circUSP34. Western blotting results showed that the expression level of vimentin and Ki‐67 decreased. Similarly, miR‐16‐5p mimic compromised the proliferation, migration, and invasion of OS cells. FISH assay results indicated that circUSP34 and miR‐16‐5p were colocalized in the cytoplasm. The sponging mechanism of circUSP34 and miR‐16‐5p was verified by dual‐luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull down assays. Interestingly, the miR‐16‐5p inhibitor partly reversed the inhibitory effect of sh‐circUSP34 on the malignancy of OS cells. Further, mice tumors for IHC indicated that vimentin, N‐cadherin, and Ki‐67 protein expression decreased, but E‐cadherin protein expression increased. Collectively, circUSP34 promoted OS malignancy, including proliferation, migration, and invasion, by sponging miR‐16‐5p. It can serve as a potential therapeutic target and biomarker. This article makes a significant contribution to our understanding of the regulation mechanisms of osteosarcoma, also considering a novel biomarker and potential therapeutic target, which would help the progression of therapeutic protocols.
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DOI：
10.18632/aging.203388
发表时间：
2021-08-13
期刊：
Aging
影响因子：
--
作者：
Liu W;Long Q;Zhang W;Zeng D;Hu B;Liu S;Chen L
通讯作者：
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影响因子：
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作者：
Zhang H;Yang K;Ren T;Huang Y;Tang X;Guo W
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影响因子：
5.2
作者：
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影响因子：
11.1
作者：
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通讯作者：
Li, Wei
DOI：
10.1177/0394632016686985
发表时间：
2017-03
影响因子：
3.5
作者：
Hou LD;Zhang J
通讯作者：
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