MiR-210-3p accelerates tumor-relevant cell functions of endometrial carcinoma by repressing RUNX1T1

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-07-01 DOI:10.1016/j.mrfmmm.2022.111793

Zhuoya Dai, Hongqin Luo, Jingdong Chen, Liang Li

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引用次数: 1

Abstract

Background

Biological mechanism of miR-210-3p in endometrial carcinoma (EC) remains unclear. Here, our purpose is to study effects of miR-210-3p on malignant progression of EC.

Methods

Bioinformatics analysis showed miRNA and mRNA are abnormally expressed in EC tissues. Quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) was utilized to compare miR-210-3p mRNA level in EC cells and tissues. qRT-PCR and western blot were used to measure RUNX1T1 and NCAM1 at mRNA and protein levels, and western blot for p-AKT and AKT proteins related to PI3K/AKT signaling pathway. Furthermore, EC cell behaviors were assayed via Cell Counting Kit-8, cell colony formation assay, wound healing, transwell and flow cytometry experiments. Interaction between RUNX1T1 and miR-210-3p was verified through dual-luciferase assay. Immunohistochemistry was used to analyze RUNX1T1 expression in clinical samples

Results

MiR-210-3p was considerably upregulated and RUNX1T1 was significantly under-expressed in EC. Overexpression of miR-210-3p stimulated cell proliferation, migration, invasion, and restrained cell apoptosis in EC. Dual-luciferase assay proved that RUNX1T1 was a target gene of miR-210-3p. The level of RUNX1T1 in EC was downregulated after overexpressing miR-210-3p. Rescue assay showed that overexpression of RUNX1T1 had an inhibitory impact on tumor-relevant cell behaviors, whereas overexpression of miR-210-3p rescued such inhibition. Overexpression of RUNX1T1 reduced p-AKT expression, which was restored with concomitantly overexpressed miR-210-3p.

Conclusion

In general, miR-210-3p behaves as an oncogene in EC by down-regulating the expression of RUNX1T1. This study elucidates a new functional mechanism in EC, and indicates miR-210-3p an underlying target.

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MiR-210-3p通过抑制RUNX1T1加速子宫内膜癌的肿瘤相关细胞功能

miR-210-3p在子宫内膜癌(EC)中的生物学机制尚不清楚。在这里，我们的目的是研究miR-210-3p对EC恶性进展的影响。方法生物信息学分析显示，EC组织中miRNA和mRNA表达异常。采用定量实时荧光聚合酶链反应(qRT-PCR)比较miR-210-3p mRNA在EC细胞和组织中的表达水平。采用qRT-PCR和western blot检测RUNX1T1和NCAM1 mRNA和蛋白水平，western blot检测PI3K/AKT信号通路相关的p-AKT和AKT蛋白。此外，通过细胞计数试剂盒-8、细胞集落形成实验、伤口愈合、transwell和流式细胞术实验检测EC细胞的行为。通过双荧光素酶测定验证RUNX1T1与miR-210-3p之间的相互作用。免疫组化分析RUNX1T1在临床样品中的表达结果:smir -210-3p在EC中显著上调，RUNX1T1在EC中显著低表达。过表达miR-210-3p刺激EC细胞增殖、迁移、侵袭，抑制细胞凋亡。双荧光素酶检测证实RUNX1T1是miR-210-3p的靶基因。过表达miR-210-3p后，EC中RUNX1T1水平下调。挽救实验显示，过表达RUNX1T1对肿瘤相关细胞行为具有抑制作用，而过表达miR-210-3p则挽救了这种抑制作用。过表达RUNX1T1可降低p-AKT的表达，同时过表达miR-210-3p可恢复p-AKT的表达。结论一般来说，miR-210-3p通过下调RUNX1T1的表达在EC中发挥致癌基因的作用。本研究阐明了EC中的一种新的功能机制，并提示miR-210-3p是潜在的靶点。

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来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.