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环状 RNA hsa_circRNA_103809 通过调控 miR-377-3p/FGFR1/ERK 轴促进肝癌发展。

Circular RNA hsa_circRNA_103809 promoted hepatocellular carcinoma development by regulating miR-377-3p/FGFR1/ERK axis.

机构信息

Department of Colorectal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.

Department of Imaging, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.

出版信息

J Cell Physiol. 2020 Feb;235(2):1733-1745. doi: 10.1002/jcp.29092. Epub 2019 Jul 17.

DOI:10.1002/jcp.29092
PMID:31317555
Abstract

In the last decade, circular RNAs (circRNAs) emerge as important regulators in multiple biological processes. Lately, it is reported hsa_circRNA_103809 could play vital parts in several types of cancers. Based on the analysis of GEO data (GSE97332), hsa_circRNA_103809 was found to be dysregulated in hepatocellular carcinoma (HCC). However, the biological function and underlying regulatory mechanisms of hsa_circRNA_103809 in HCC remain unclear. Our results suggested that hsa_circRNA_103809 was overexpressed in HCC patients, and hsa_circRNA_103809 knockdown remarkably inhibited the proliferation, cycle progression, and migration of HCC cells. The investigations of molecular showed that hsa_circRNA_103809 could elevate the protein expression of a miR-377-3p target, fibroblast growth factor receptor 1 (FGFR1), through interacting with miR-377-3p and decreasing its expression level. Additionally, in vivo assays revealed hsa_circRNA_103809 short hairpin RNA served as a tumor suppressor through downregulating FGFR1 in HCC. This study systematically investigated novel regulatory signaling of hsa_circRNA_103809/miR-377-3p/FGFR1 axis, providing insights into hepatocellular carcinoma treatment from bench to clinic.

摘要

在过去的十年中,环状 RNA(circRNAs)作为多种生物学过程中的重要调节剂而出现。最近,据报道 hsa_circRNA_103809 可以在几种类型的癌症中发挥重要作用。基于 GEO 数据(GSE97332)的分析,发现 hsa_circRNA_103809 在肝细胞癌(HCC)中失调。然而,hsa_circRNA_103809 在 HCC 中的生物学功能和潜在的调节机制仍不清楚。我们的研究结果表明,hsa_circRNA_103809 在 HCC 患者中表达上调,hsa_circRNA_103809 敲低显著抑制 HCC 细胞的增殖、周期进展和迁移。分子研究表明,hsa_circRNA_103809 通过与 miR-377-3p 相互作用并降低其表达水平,可上调 miR-377-3p 靶标纤维母细胞生长因子受体 1(FGFR1)的蛋白表达。此外,体内实验表明 hsa_circRNA_103809 短发夹 RNA 通过下调 HCC 中的 FGFR1 发挥肿瘤抑制作用。本研究系统地研究了 hsa_circRNA_103809/miR-377-3p/FGFR1 轴的新的调节信号,为从实验室到临床的肝细胞癌治疗提供了新的见解。

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