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环状 RNA 0038718 通过调控 miR-761/miR-214-3p/ITGA6 轴促进结直肠癌的进展。

Circ_0038718 augments colorectal cancer progression through mediating the miR-761/miR-214-3p/ITGA6 axis.

机构信息

Department of Pathology, He Nan Provincial People's Hospital, Zhengzhou, Henan, China; Department of Pathology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Pathology, People's Hospital of Henan University, Zhengzhou, Henan, China.

Department of Pathology, He Nan Provincial People's Hospital, Zhengzhou, Henan, China; Department of Pathology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Pathology, People's Hospital of Henan University, Zhengzhou, Henan, China.

出版信息

Pathol Res Pract. 2024 Nov;263:155649. doi: 10.1016/j.prp.2024.155649. Epub 2024 Oct 9.

Abstract

BACKGROUND

Accumulating studies have disclosed that circular RNAs (circRNAs) are closely associated with the malignant progression of colorectal cancer (CRC). The aim of our work was to reveal the function of circ_0038718 in CRC.

METHODS

The level of genes and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. In vitro researches were executed via utilizing cell counting Kit-8 (CCK-8), EdU, flow cytometry analysis and wound-healing assay, individually. The target relationship was validated by Dual-luciferase reporter assay. In vivo assay was employed through establishing xenograft tumor model.

RESULTS

Circ_0038718 was identified to be increased in CRC tissues and cells. Circ_0038718 downregulation suppressed cell proliferation, migration and facilitated apoptosis of CRC. Mechanistically, circ_0038718 could sponge miR-761 and miR-214-3p to modulate the expression of ITGA6. The rescue experiments proved that miR-761 or miR-214-3p inhibitor attenuated the repressive impact of circ_0038718 inhibition on CRC cells progression, and overexpressed ITGA6 could weaken the inhibitory effect of miR-761 or miR-214-3p on tumor cells. Furthermore, depletion of circ_0038718 confined the tumor growth in vivo.

CONCLUSION

Circ_0038718 aggravated the progression of CRC cells via mediating ITGA6 expression through targeting miR-761 and miR-214-3p, providing a new therapeutic target for CRC patients.

摘要

背景

越来越多的研究表明,环状 RNA(circRNAs)与结直肠癌(CRC)的恶性进展密切相关。我们的工作旨在揭示 circ_0038718 在 CRC 中的功能。

方法

通过实时定量聚合酶链反应(qRT-PCR)和蛋白质印迹法评估基因和蛋白质水平。通过细胞计数试剂盒-8(CCK-8)、EdU、流式细胞术分析和划痕愈合实验分别进行体外研究。通过双荧光素酶报告基因实验验证靶标关系。通过建立异种移植肿瘤模型进行体内实验。

结果

Circ_0038718 在 CRC 组织和细胞中被鉴定为上调。Circ_0038718 下调抑制 CRC 细胞增殖、迁移并促进细胞凋亡。机制上,circ_0038718 可以海绵吸附 miR-761 和 miR-214-3p,调节 ITGA6 的表达。挽救实验证明,miR-761 或 miR-214-3p 抑制剂减弱了 circ_0038718 抑制对 CRC 细胞进展的抑制作用,过表达 ITGA6 可以减弱 miR-761 或 miR-214-3p 对肿瘤细胞的抑制作用。此外,circ_0038718 的耗竭限制了体内肿瘤的生长。

结论

Circ_0038718 通过靶向 miR-761 和 miR-214-3p 介导 ITGA6 表达,加重 CRC 细胞的进展,为 CRC 患者提供了新的治疗靶点。

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