Long non-coding RNA linc00659 promotes tumour progression by regulating FZD6/Wnt/β-catenin signalling pathway in colorectal cancer via m6A reader IGF2BP1

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2023-11-27 DOI:10.1002/jgm.3636

Shufen Xu, Zichun Liu, Qian Luo, Lisha Chang, Jie Ding, Yanan Xiao, Yangyang Zhang, Guoren Zhou, Keming Wang

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引用次数: 0

Abstract

Background

Abnormal N6-methyladenosine (m6A) modification has become a driving factor in tumour development and progression. The linc00659 is abnormally highly expressed in digestive tract tumours and promotes cancer progression, but there is little research on the mechanism of linc00659 and m6A.

Methods

The expression of linc00659 in colorectal cancer (CRC) tissues and cells was assessed by a quantitative real-time PCR. The proliferative capacity of CRC cells was determined by colony formation, Cell Counting Kit-8 and 5-ethynyl-2 deoxyuridine assays, and the migratory capacity of CRC was determined by wound healing and transwell assays and tube formation. In vivo, a xenograft tumour model was used to detect the effect of linc00659 on tumour growth. The Wnt/β-catenin signalling pathway and related protein expression levels were measured by western blotting. The binding of linc00659 to insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was assessed by RNA pull-down and an immunoprecipitation assay. The effect of IGF2BP1 on FZD6 was detected by an RNA stability assay.

Results

The expression of linc00659 was abnormally elevated in CRC tissues and cells compared to normal colonic tissues and cells. We confirm that linc00659 promotes the growth of CRC cells both in vivo and in vitro. Mechanistically, linc00659 binds to IGF2BP1 and specifically enhances its activity to stabilize the target gene FZD6. Therefore, linc00659 and IGF2BP1 activate the Wnt/β-catenin signalling pathway, promoting cell proliferation in CRC.

Conclusions

Our results show that linc00659 and IGF2BP1 cooperate to promote the stability of the target FZD6 mRNA, thereby facilitating CRC progression, which may represent a potential diagnostic, prognostic and therapeutic target for CRC.

Abstract Image

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长链非编码RNA linc00659通过m6A读取器IGF2BP1调控结直肠癌FZD6/Wnt/β-catenin信号通路，促进肿瘤进展。

背景:n6 -甲基腺苷(m6A)异常修饰已成为肿瘤发生发展的驱动因素。linc00659在消化道肿瘤中异常高表达，促进肿瘤进展，但对linc00659与m6A的作用机制研究甚少。方法:采用实时荧光定量PCR法检测结直肠癌组织和细胞中linc00659的表达。通过集落形成、细胞计数试剂盒-8和5-乙基-2脱氧尿苷测定结直肠癌细胞的增殖能力，通过伤口愈合、通孔试验和小管形成测定结直肠癌细胞的迁移能力。在体内，采用异种移植肿瘤模型检测linc00659对肿瘤生长的影响。western blotting检测Wnt/β-catenin信号通路及相关蛋白表达水平。通过RNA拉下和免疫沉淀法评估linc00659与胰岛素样生长因子2 mrna结合蛋白1 (IGF2BP1)的结合。通过RNA稳定性实验检测IGF2BP1对FZD6的影响。结果:与正常结肠组织细胞相比，结直肠癌组织细胞中linc00659的表达异常升高。我们证实linc00659在体内和体外都能促进CRC细胞的生长。从机制上讲，linc00659与IGF2BP1结合并特异性增强其活性以稳定靶基因FZD6。因此，linc00659和IGF2BP1激活Wnt/β-catenin信号通路，促进结直肠癌细胞增殖。结论:我们的研究结果表明，linc00659和IGF2BP1共同促进了靶基因FZD6 mRNA的稳定性，从而促进了CRC的进展，这可能是CRC潜在的诊断、预后和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.