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长链非编码RNA FLJ33360通过靶向miRNA-140/MMP9轴促进肝细胞癌转移。

LncRNA FLJ33360 accelerates the metastasis in hepatocellular carcinoma by targeting miRNA-140/MMP9 axis.

作者信息

Lu Zhenhui, Yu Yingzi, Ding Xiangchun, Jin Dong, Wang Genwang, Zhou Yu, Zhu Yongzhao, Na Li, He Yaqin, Wang Qi

机构信息

Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University Yinchuan, Ningxia, China.

Department of Infection Control, General Hospital of Ningxia Medical University Yinchuan, Ningxia, China.

出版信息

Am J Transl Res. 2020 Feb 15;12(2):583-591. eCollection 2020.

Abstract

This study aims to detect expression level of long non-coding RNA (lncRNA) FLJ33360 in hepatocellular carcinoma (HCC) and its regulatory effects on accelerating malignant progression of HCC. Expression levels of FLJ33360 in 29 matched HCC tissues and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection of sh-FLJ33360#1 in Bel-7402 and HepG2 cells, changes in migratory and invasive capacities were evaluated by Transwell and wound healing assay. Potential miRNAs targeting FLJ33360 were verified. The correlation between expression levels of FLJ33360 and miRNA-140 in HCC tissues was determined. At last, potential influences of FLJ33360/miRNA-140 regulatory loop on HCC phenotypes were determined by rescue experiments. FLJ33360 was upregulated in HCC tissues relative to paracancerous ones. After knockdown of FLJ33360, migratory and invasive capacities in Bel-7402 and HepG2 cells were attenuated. There were five miRNA candidates predicted to bind FLJ33360, and miRNA-140 was the most differentially expressed by FLJ33360 regulation. Dual-luciferase reporter gene assay confirmed the binding between FLJ33360 and miRNA-140. Besides, their expression levels were negatively correlated in HCC tissues. Moreover, knockdown of miRNA-140 could stimulate metastatic ability in HCC. At last, rescue experiments verified the involvement of miRNA-140 in FLJ33360-regulated HCC progression. LncRNA FLJ33360 is upregulated in HCC. It accelerates the metastasis of HCC through targeting miRNA-140/MMP9 axis.

摘要

本研究旨在检测长链非编码RNA(lncRNA)FLJ33360在肝细胞癌(HCC)中的表达水平及其对HCC恶性进展的调控作用。采用定量实时聚合酶链反应(qRT-PCR)检测29对匹配的HCC组织和癌旁组织中FLJ33360的表达水平。在Bel-7402和HepG2细胞中转染sh-FLJ33360#1后,通过Transwell和伤口愈合试验评估迁移和侵袭能力的变化。验证了靶向FLJ33360的潜在微小RNA(miRNA)。确定了HCC组织中FLJ33360与miRNA-140表达水平之间的相关性。最后,通过挽救实验确定FLJ33360/miRNA-140调控环对HCC表型特征的潜在影响。与癌旁组织相比,FLJ33360在HCC组织中表达上调。敲低FLJ33360后,Bel-7402和HepG2细胞的迁移和侵袭能力减弱。预测有5种miRNA候选物可与FLJ33360结合,其中miRNA-140受FLJ33360调控的差异表达最为明显。双荧光素酶报告基因试验证实了FLJ33360与miRNA-140之间的结合。此外,它们在HCC组织中的表达水平呈负相关。此外,敲低miRNA-140可促进HCC的转移能力。最后,挽救实验证实miRNA-140参与了FLJ

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