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环状WDR78通过调控miR-653-3p/RGS4轴抑制结直肠癌的发展。

CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis.

作者信息

Hao Chu, Pu Yunju, Li Jiunian, Zhong Zhi, Huang Zhaohui, Wang Xue

机构信息

Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, China.

Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.

出版信息

J Cancer Res Clin Oncol. 2025 Feb 6;151(2):66. doi: 10.1007/s00432-025-06092-2.

Abstract

BACKGROUND

Colorectal cancer (CRC) stands as one of the most serious threats to human health, with its mortality rate increase during the past years. Low diagnostic accuracy, poor prognosis, and high recurrence rates attributed to the high mortality rate of CRC. Consequently, the urgency to identify potential diagnose and biological targets for intervention in this disease. Among the various molecular factor associated with this disease, circular RNAs (circRNAs) have been a hot topic. These noncoding RNA molecules, characterized by their unique closed loop structure, displayed close associations with the progression of tumors.

METHODS

Actinomycin D experiment and RNA digestion experiment were used to verify the circular structure characteristics of circWDR78. Proliferation and motility ability of circWDR78 was evaluated by in vitro functional experiment. We also used RNA-seq technology to explore the signal pathways and genes it might regulate. Finally, the luciferase assay and qRT-PCR experiment proved that circWDR78 could sponge miR-653-3p, and confirmed that RGS4 is the downstream target of miR-653-3p.

RESULTS

This study demonstrated that circWDR78 is lower expression in colorectal cancer tissues, revealing its capacity to inhibit proliferation, colony forming ability and cell motility. These findings hint at a potential correlation between its downregulation and the progression of CRC. Mechanistically, we found that circWDR78 could sponge miR-653-3p and identified RGS4 as a novel target of miR-653-3p.

CONCLUSION

This discovery highlights the significance of circWDR78 as a potential regulatory axis of miR-653-3p/RGS4 in CRC progression.

摘要

背景

结直肠癌(CRC)是对人类健康最严重的威胁之一,其死亡率在过去几年中有所上升。低诊断准确性、不良预后和高复发率导致了结直肠癌的高死亡率。因此,迫切需要确定针对该疾病进行干预的潜在诊断和生物学靶点。在与该疾病相关的各种分子因素中,环状RNA(circRNAs)一直是一个热门话题。这些非编码RNA分子具有独特的闭环结构,与肿瘤进展密切相关。

方法

使用放线菌素D实验和RNA消化实验来验证circWDR78的环状结构特征。通过体外功能实验评估circWDR78的增殖和运动能力。我们还使用RNA测序技术探索其可能调节的信号通路和基因。最后,荧光素酶报告基因检测和qRT-PCR实验证明circWDR78可以吸附miR-653-3p,并证实RGS4是miR-653-3p的下游靶点。

结果

本研究表明circWDR78在结直肠癌组织中表达较低,揭示了其抑制增殖、集落形成能力和细胞运动的能力。这些发现暗示其下调与结直肠癌进展之间可能存在关联。从机制上讲,我们发现circWDR78可以吸附miR-653-3p,并确定RGS4是miR-653-3p的一个新靶点。

结论

这一发现突出了circWDR78作为miR-653-3p/RGS4在结直肠癌进展中的潜在调控轴的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dbe/11802675/09840c28edd2/432_2025_6092_Fig1_HTML.jpg

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