Circ_0004585 Facilitates Tumorigenesis of Colorectal Cancer Via Modulating the miR-338-3p/ZFX Axis and Activating the MEK/ERK Pathway.

IF 2.3 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2023-04-01 DOI:10.1007/s12195-022-00756-6

Zenghai Lin, Jianwei Lin

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引用次数: 0

Abstract

Background: Colorectal cancer (CRC) is a common malignant tumor in the digestive tract. Circular RNAs (circRNAs) have been identified as crucial regulators of tumorigenesis. However, the role and potential mechanism of circ_0004585 in CRC are poorly understood.

Methods: The expression of circ_0004585, microRNA-338-3p (miR-338-3p), and zinc finger protein X-linked (ZFX) was detected by quantitative real-time PCR and Western blot. Cell proliferation, cell cycle arrest, apoptosis, and angiogenesis were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry and tube formation assays. Western blot assay was applied to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins and MEK/ERK signaling pathway-related proteins. A xenograft model was used to analyze tumor growth in vivo. The targeted relationship between miR-338-3p and circ_0004585/ZFX was verified by a dual-luciferase reporter assay.

Results: Circ_0004585 and ZFX were up-regulated, while miR-338-3p was down-regulated in CRC tissues and cells. Silencing of circ_0004585 inhibited proliferation, angiogenesis, and EMT and triggered apoptosis in CRC cells. Consistently, circ_0004585 depletion blocked tumor growth in vivo. Circ_0004585 contributed to CRC cell development via sequestering miR-338-3p. Also, miR-338-3p hindered the malignant progression of CRC cells by targeting ZFX. Circ_0004585 activated MEK/ERK pathway via regulating ZFX.

Conclusion: Circ_0004585 facilitated CRC progression through modulating miR-338-3p/ZFX/MEK/ERK pathway, which might provide a potential therapeutic target for CRC.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-022-00756-6.

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Circ_0004585通过调节miR-338-3p/ZFX轴和激活MEK/ERK通路促进结直肠癌的发生。

背景:结直肠癌(Colorectal cancer, CRC)是消化道常见的恶性肿瘤。环状rna (circRNAs)已被确定为肿瘤发生的关键调节因子。然而，circ_0004585在CRC中的作用和潜在机制尚不清楚。方法:采用实时荧光定量PCR和Western blot检测circ_0004585、microRNA-338-3p (miR-338-3p)和锌指蛋白X-linked (ZFX)的表达。采用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2- h -溴化四唑(MTT)、5-乙基-2'-脱氧尿苷(EdU)、流式细胞术和成管实验评估细胞增殖、细胞周期阻滞、细胞凋亡和血管生成。Western blot检测上皮间质转化(epithelial-mesenchymal transition, EMT)相关蛋白和MEK/ERK信号通路相关蛋白的表达。采用异种移植物模型分析肿瘤在体内的生长情况。miR-338-3p与circ_0004585/ZFX之间的靶向关系通过双荧光素酶报告基因实验得到验证。结果:Circ_0004585和ZFX在结直肠癌组织和细胞中上调，miR-338-3p下调。circ_0004585的沉默抑制了CRC细胞的增殖、血管生成和EMT，并引发了细胞凋亡。在体内，circ_0004585的消耗一致地阻断了肿瘤的生长。Circ_0004585通过隔离miR-338-3p促进CRC细胞发育。此外，miR-338-3p通过靶向ZFX抑制CRC细胞的恶性进展。Circ_0004585通过调节ZFX激活MEK/ERK通路。结论:Circ_0004585通过调节miR-338-3p/ZFX/MEK/ERK通路促进CRC进展，可能为CRC提供潜在的治疗靶点。补充信息:在线版本包含补充资料，提供地址为10.1007/s12195-022-00756-6。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.