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长链非编码RNA SNHG7通过miR-122-5p/FOXK2轴促进肝癌进展。

LncRNA SNHG7 Promotes the HCC Progression Through miR-122-5p/FOXK2 Axis.

作者信息

Zhao Zhengbin, Gao Jing, Huang Shuangsheng

机构信息

Department of Infectious Diseases, The First Hospital of Lanzhou University, No. 1 Donggang West Road, Chengguan District, Lanzhou City, Gansu, China.

Department of Laboratory, Hospital of Northwest Minzu University, Lanzhou, 730030, Gansu, China.

出版信息

Dig Dis Sci. 2022 Mar;67(3):925-935. doi: 10.1007/s10620-021-06918-2. Epub 2021 Mar 18.

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor with high mortality and severe complication in China. Numerous studies have shown that long noncoding RNAs (lncRNAs) are involved in the regulation of various processes in cancer cells. Our research aimed to investigate the underlying mechanism of the lncRNA small nucleolar RNA host gene 7 (SNHG7) in HCC development. The expression of SNHG7, microRNA-122-5p (miR-122-5p), and Forkhead box K2 (FOXK2) was assessed via quantitative real-time polymerase chain reaction. 3-(4,5) -dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and transwell assays were performed to measure cell viability, migration, and invasion, respectively. The relative protein levels were detected by Western blot. The relationships between miR-122-5p and SNHG7 or FOXK2 were predicted by online software and then confirmed by dual-luciferase reporter assay. Animal experiments were conducted to clarify the effects of SNHG7 on proliferation in vivo. To begin with, SNHG7 was upregulated, while miR-122-5p was downregulated in HCC tissues and cells. Downregulation of SNHG7 inhibited cell growth and metastasis. Interestingly, SNHG7 could abolish the effects of miR-122-5p on HCC cells. Furthermore, miR-122-5p targeted FOXK2 and miR-122-5p recovered the effects of FOXK2 downregulation on cell growth and metastasis in HCC cells. Besides, SNHG7 facilitated HCC tumor growth in vivo through the miR-122-5p/FOXK2 axis. The lncRNA SNHG7 boosted the development of HCC by regulating FOXK2 through sponging miR-122-5p.

摘要

肝细胞癌(HCC)在中国是一种死亡率高且并发症严重的恶性肿瘤。大量研究表明,长链非编码RNA(lncRNAs)参与癌细胞各种过程的调控。我们的研究旨在探究lncRNA小核仁RNA宿主基因7(SNHG7)在HCC发生发展中的潜在机制。通过定量实时聚合酶链反应评估SNHG7、微小RNA-122-5p(miR-122-5p)和叉头框K2(FOXK2)的表达。分别进行3-(4,5)-二甲基噻唑-2,5-二苯基四氮唑溴盐(MTT)和Transwell实验来检测细胞活力、迁移和侵袭能力。通过蛋白质免疫印迹法检测相关蛋白的相对水平。利用在线软件预测miR-122-5p与SNHG7或FOXK2之间的关系,然后通过双荧光素酶报告基因实验进行验证。开展动物实验以阐明SNHG7对体内增殖的影响。首先,在HCC组织和细胞中SNHG7表达上调,而miR-122-5p表达下调。SNHG7的下调抑制细胞生长和转移。有趣的是,SNHG7可消除miR-122-5p对HCC细胞的影响。此外,miR-122-5p靶向FOXK2,且miR-122-5p可恢复FOXK2下调对HCC细胞生长和转移的影响。此外,SNHG7通过miR-122-5p/FOXK2轴促进体内HCC肿瘤生长。lncRNA SNHG7通过海绵吸附miR-122-5p调控FOXK2,从而促进HCC的发展。

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