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上调通过与 miR-139-5p 的竞争性结合来激活表达,从而促进肝细胞癌的进展。

Up-regulation of activates expression by competitive binding to miR-139-5p to promote hepatocellular carcinoma progression.

机构信息

a Department of Hepatobiliary Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu , Sichuan , China.

b Department of Ultrasound, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu , Sichuan , China.

出版信息

Cell Cycle. 2019 Aug;18(16):1849-1867. doi: 10.1080/15384101.2019.1629772. Epub 2019 Jul 1.

Abstract

We aimed to assess the roles of small nucleolar RNA host gene 6 () in hepatocellular carcinoma (HCC) progression, and establish the lncRNA-miRNA-mRNA regulation mechanism for HCC therapy. is one of the host genes in small nucleolar RNAs (snoRNAs), which make a difference in the development of human cancers. is a gene encoding a member of the serpin superfamily of serine proteinase inhibitors with miRNA predicted by TargetScan and DIANA Tools. , serpin family H member 1 () and miR-139-5p expression levels in HCC tissues and cells were determined by quantitative real-time PCR (qRT-PCR). Migration and invasion of HCC cells were measured by transwell assay. Cell cycle analysis was determined by using flow cytometry. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and colony formation assay were performed for cell viability analysis. The expression of was detected by qRT-PCR and western blot. Dual-luciferase reporter gene assay was conducted to identify the targeted relationship between miR-139-5p and , as well as and miR-139-5p. The positive regulation between and was demonstrated in this study. In contrast, miR-139-5p was significantly down-regulated in HCC cells, the inhibition of miR-139-5p promotes the proliferation of HCC cells, and accelerated the cell cycle of HCC cells. Our study demonstrated the co-expression of and in HCC cells for the first time, which revealed that could serve as a novel oncogene for the HCC therapy by its regulation.

摘要

我们旨在评估小核仁 RNA 宿主基因 6 () 在肝细胞癌 (HCC) 进展中的作用,并建立用于 HCC 治疗的 lncRNA-miRNA-mRNA 调控机制。 是小核仁 RNA (snoRNAs) 的宿主基因之一,在人类癌症的发展中起着重要作用。 是编码丝氨酸蛋白酶抑制剂丝氨酸蛋白酶抑制剂超家族成员的基因,靶标扫描和 DIANA 工具预测了 miRNA。通过定量实时 PCR (qRT-PCR) 测定 HCC 组织和细胞中的 、丝氨酸蛋白酶家族 H 成员 1 () 和 miR-139-5p 的表达水平。通过 Transwell 测定法测定 HCC 细胞的迁移和侵袭。通过流式细胞术测定细胞周期分析。3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐 (MTT) 测定法和集落形成测定法用于细胞活力分析。通过 qRT-PCR 和 Western blot 检测 的表达。进行双荧光素酶报告基因测定以鉴定 miR-139-5p 与 之间以及 与 miR-139-5p 之间的靶向关系。本研究证实了 与 之间的正调控关系。相反,miR-139-5p 在 HCC 细胞中显著下调,miR-139-5p 的抑制促进了 HCC 细胞的增殖,并加速了 HCC 细胞的细胞周期。我们的研究首次证明了 HCC 细胞中 的共表达,这表明 通过其调控, 可以作为 HCC 治疗的新型癌基因。

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