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环状 RNA_100859 通过海绵吸附 miR-217-HIF-1α 通路在结肠癌中发挥癌基因作用。

circRNA_100859 functions as an oncogene in colon cancer by sponging the miR-217-HIF-1α pathway.

机构信息

Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.

Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Aging (Albany NY). 2020 Jul 8;12(13):13338-13353. doi: 10.18632/aging.103438.

DOI:10.18632/aging.103438
PMID:32644049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7377858/
Abstract

Circular RNAs (circRNAs) play an important role in cancer development and progression by regulating gene expression. The present study aimed to investigate the function of circRNA_100859 in colon cancer. circRNA expression profiles from a human circRNAs chip were analyzed. The effects of circRNA_100859 on cell proliferation and apoptosis were assessed and interactions between circRNA_100859 and its micro (mi)RNA and target genes were analyzed. The diagnostic and prognostic significance of circRNA_100859 was also investigated. It was identified that circRNA_100859 was overexpressed in colon cancer tissues and promoted cell proliferation and inhibited cell apoptosis. Additionally, bioinformatics and a dual-luciferase reporter assay confirmed that circRNA_100859 acted as a miR-217 sponge, and miR-217 directly targeted hypoxia-inducible factor (HIF)-1α. Rescue assays demonstrated that HIF-1α protein and mRNA expression levels and cell proliferation were regulated by the circRNA_100859/miR-217 axis (<0.05). Furthermore, statistical analysis showed that the circRNA_100859-miR-217-HIF-1α axis was associated with Tumor-Node-Metastasis (TNM) stage, histological grade, and KRAS mutations, and also showed high diagnostic and prognostic value for patients with colon cancer (<0.05). Therefore, it was concluded that circRNA_100859 functions as an oncogene in colon cancer by sponging the miR-217-HIF-1α pathway. In addition, the circRNA_100859-miR-217-HIF-1α axis may serve as a novel diagnostic and prognostic biomarker for patients with colon cancer.

摘要

环状 RNA（circRNAs）通过调节基因表达在癌症的发生和发展中发挥重要作用。本研究旨在探讨 circRNA_100859 在结肠癌中的功能。分析了人类 circRNAs 芯片中的 circRNA 表达谱。评估了 circRNA_100859 对细胞增殖和凋亡的影响，并分析了 circRNA_100859 与其 micro（mi）RNA 和靶基因之间的相互作用。还研究了 circRNA_100859 的诊断和预后意义。结果表明，circRNA_100859 在结肠癌组织中表达上调，并促进细胞增殖，抑制细胞凋亡。此外，生物信息学和双荧光素酶报告基因实验证实，circRNA_100859 作为 miR-217 的海绵，miR-217 直接靶向缺氧诱导因子（HIF）-1α。挽救实验表明，circRNA_100859 通过 circRNA_100859/miR-217 轴调节 HIF-1α 蛋白和 mRNA 表达水平及细胞增殖（<0.05）。此外，统计分析表明，circRNA_100859-miR-217-HIF-1α 轴与肿瘤-淋巴结-转移（TNM）分期、组织学分级和 KRAS 突变有关，并且对结肠癌患者具有较高的诊断和预后价值（<0.05）。因此，结论是 circRNA_100859 通过海绵吸附 miR-217-HIF-1α 通路在结肠癌中发挥癌基因作用。此外，circRNA_100859-miR-217-HIF-1α 轴可能成为结肠癌患者新的诊断和预后生物标志物。

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