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环状RNA circDCUN1D4通过靶向miR-590-5p/TIMP3轴抑制肝细胞癌发展。

Circular RNA circDCUN1D4 suppresses hepatocellular carcinoma development via targeting the miR-590-5p/ TIMP3 axis.

作者信息

Li Hongyu, Su Bing, Jiang Yan, Zhang Boyang, Du Rulong, Song Can, Hou Bin, Xu Kun, Wu Lida, Gu Yuchun

机构信息

College of Chemistry and Lie Science, Beijing University of Technology, Beijing, 100124, China.

Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China.

出版信息

Mol Cancer. 2025 Mar 25;24(1):95. doi: 10.1186/s12943-025-02300-2.

DOI:10.1186/s12943-025-02300-2
PMID:40128740
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11934760/
Abstract

Hepatocellular carcinoma (HCC) is a major global health concern, necessitating innovative therapeutic strategies. In this study, we investigated the functional role of circular RNA circDCUN1D4 in HCC progression and its potential therapeutic implications. It was found that HCC patients exhibiting higher levels of circDCUN1D4 demonstrated a more favorable survival rate. Furthermore, we revealed that circDCUN1D4 suppressed HCC cell proliferation, migration, and invasion. Mechanistically, circDCUN1D4 was identified as a sponge for miR-590-5p, leading to the downregulation of its downstream target, Tissue Inhibitor of Metalloproteinase 3 (TIMP3). Importantly, circDCUN1D4 administration through In vivo jet-PEI exhibited a robust inhibitory effect on tumor progression without causing notable toxicity in mice. Overall, our findings highlight circDCUN1D4 as a promising therapeutic candidate for HCC, unraveling its intricate regulatory role through the miR-590-5p/TIMP3 axis. This study contributes valuable insights into the potential clinical applications of circRNA-based therapies for HCC.

摘要

肝细胞癌（HCC）是一个重大的全球健康问题，需要创新的治疗策略。在本研究中，我们调查了环状RNA circDCUN1D4在HCC进展中的功能作用及其潜在的治疗意义。研究发现，circDCUN1D4水平较高的HCC患者生存率更高。此外，我们发现circDCUN1D4抑制HCC细胞的增殖、迁移和侵袭。机制上，circDCUN1D4被确定为miR-590-5p的海绵，导致其下游靶点金属蛋白酶组织抑制剂3（TIMP3）的下调。重要的是，通过体内jet-PEI给药circDCUN1D4对肿瘤进展具有强大的抑制作用，且在小鼠中未引起明显毒性。总体而言，我们的研究结果突出了circDCUN1D4作为HCC有前景的治疗候选物，通过miR-590-5p/TIMP3轴揭示了其复杂的调节作用。本研究为基于circRNA的HCC治疗的潜在临床应用提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/d7de8f89e34a/12943_2025_2300_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/37dca5d03345/12943_2025_2300_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/d7de8f89e34a/12943_2025_2300_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/37dca5d03345/12943_2025_2300_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/6498d2e202bf/12943_2025_2300_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/d5706f4b07e0/12943_2025_2300_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/279b603364f6/12943_2025_2300_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/a3eae42d8715/12943_2025_2300_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/7df1b7054573/12943_2025_2300_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/8eb388af7aa5/12943_2025_2300_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acbf/11934760/d7de8f89e34a/12943_2025_2300_Fig8_HTML.jpg

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