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骨肉瘤中circ_0076684的上调通过介导miRNAs/CUX1促进恶性进展。

Upregulation of circ_0076684 in osteosarcoma facilitates malignant processes by mediating miRNAs/CUX1.

作者信息

Cai Pengfei, Fu Xin, Li Xiaofei, Zhao Wei

机构信息

Department of Orthopeadics, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No. 365 Renmin East Road, Jinhua City, 321000, Zhejiang Province, China.

出版信息

J Orthop Surg Res. 2024 Apr 24;19(1):260. doi: 10.1186/s13018-024-04742-8.

DOI:10.1186/s13018-024-04742-8
PMID:38659042
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11044396/
Abstract

Circular RNAs (circRNAs) are a newly appreciated type of endogenous noncoding RNAs that play vital roles in the development of various human cancers, including osteosarcoma (OS). In this study, we investigated three circRNAs (circ_0076684, circ_0003563, circ_0076691) from the RUNX Family Transcription Factor 2 (RUNX2) gene locus in OS. We found that the expression of circ_0076684, circ_0003563, circ_0076691, and RUNX2 mRNA is upregulated in OS, which is a consequence of CBX4-mediated transcriptional activation. Among these three RUNX2-circRNAs, only circ_0076684 is significantly associated with the clinical features and prognosis of OS patients. Functional experiments indicate that circ_0076684 promotes OS progression in vitro and in vivo. Circ_0076684 acts as a sponge for miR-370-3p, miR-140-3p, and miR-193a-5p, raising Cut Like Homeobox 1 (CUX1) expression by sponging these three miRNAs. Furthermore, we presented that circ_0076684 facilitates OS progression via CUX1. In conclusion, this study found that the expression of three circRNAs and RUNX2 mRNA from the RUNX2 gene locus is significantly upregulated in OS, as a result of CBX4-mediated transcriptional activation. Circ_0076684 raises CUX1 expression by sponging miR-370-3p, miR-140-3p, and miR-193a-5p, and facilitates OS progression via CUX1.

摘要

环状RNA（circRNAs）是一类新发现的内源性非编码RNA，在包括骨肉瘤（OS）在内的多种人类癌症的发展中发挥着至关重要的作用。在本研究中，我们调查了骨肉瘤中来自RUNX家族转录因子2（RUNX2）基因位点的三种环状RNA（circ_0076684、circ_0003563、circ_0076691）。我们发现，circ_0076684、circ_0003563、circ_0076691和RUNX2 mRNA在骨肉瘤中的表达上调，这是CBX4介导的转录激活的结果。在这三种RUNX2环状RNA中，只有circ_0076684与骨肉瘤患者的临床特征和预后显著相关。功能实验表明，circ_0076684在体外和体内均促进骨肉瘤进展。Circ_0076684作为miR-370-3p、miR-140-3p和miR-193a-5p的海绵，通过吸附这三种微小RNA提高了Cut Like同源框1（CUX1）的表达。此外，我们还提出circ_0076684通过CUX1促进骨肉瘤进展。总之，本研究发现，由于CBX4介导的转录激活，RUNX2基因位点的三种环状RNA和RUNX2 mRNA在骨肉瘤中的表达显著上调。Circ_0076684通过吸附miR-370-3p、miR-140-3p和miR-193a-5p提高CUX1表达，并通过CUX1促进骨肉瘤进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/89ddedc3d214/13018_2024_4742_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/0be436aec2b0/13018_2024_4742_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/5fb0537f700b/13018_2024_4742_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/1a6eb764cf60/13018_2024_4742_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/bf39837e5dc4/13018_2024_4742_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/5ca41de2a9dd/13018_2024_4742_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/89ddedc3d214/13018_2024_4742_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/0be436aec2b0/13018_2024_4742_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/5fb0537f700b/13018_2024_4742_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/1a6eb764cf60/13018_2024_4742_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/bf39837e5dc4/13018_2024_4742_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/5ca41de2a9dd/13018_2024_4742_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/11044396/89ddedc3d214/13018_2024_4742_Fig6_HTML.jpg

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