Circ_0038718 通过介导 miR-761/miR-214-3p/ITGA6 轴促进结直肠癌进展

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2024-10-09 DOI:10.1016/j.prp.2024.155649

Daohong Li , Yuwei Jin , Jinxing Hu , Hui He , Aixia Hu

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引用次数: 0

摘要

背景越来越多的研究表明，环状RNA（circRNA）与结直肠癌（CRC）的恶性进展密切相关。方法通过实时定量聚合酶链反应（qRT-PCR）和免疫印迹法评估基因和蛋白质水平。体外研究分别采用细胞计数试剂盒-8（CCK-8）、EdU、流式细胞仪分析和伤口愈合试验。目标关系通过双荧光素酶报告实验进行了验证。通过建立异种移植肿瘤模型进行体内检测。结果发现，Circ_0038718 在 CRC 组织和细胞中增高，下调 Circ_0038718 可抑制 CRC 的细胞增殖、迁移并促进细胞凋亡。从机理上讲，circ_0038718可以通过海绵状的miR-761和miR-214-3p来调节ITGA6的表达。拯救实验证明，miR-761或miR-214-3p抑制剂可减弱circ_0038718抑制剂对CRC细胞进展的抑制作用，而过表达的ITGA6可减弱miR-761或miR-214-3p对肿瘤细胞的抑制作用。结论circ_0038718通过靶向miR-761和miR-214-3p，介导ITGA6的表达，从而加剧了CRC细胞的进展，为CRC患者提供了一个新的治疗靶点。

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

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.

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.