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GFI1介导的LINC00675作为ceRNA上调通过海绵化miR-942-5p抑制肝细胞癌转移

GFI1-Mediated Upregulation of LINC00675 as a ceRNA Restrains Hepatocellular Carcinoma Metastasis by Sponging miR-942-5p.

作者信息

Lu Libai, Li Shubo, Zhang Ying, Luo Zongjiang, Chen Yichen, Ma Jiasheng, Chen Pengyu, Wang Wei, Pu Jian, Wang Jianchu

机构信息

Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

Department of Biochemistry and Molecular Biology, Youjiang Medical University for Nationalities, Baise, China.

出版信息

Front Oncol. 2021 Jan 8;10:607593. doi: 10.3389/fonc.2020.607593. eCollection 2020.

DOI:10.3389/fonc.2020.607593
PMID:33489916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7820889/
Abstract

Hepatocellular carcinoma (HCC) is a common malignant liver tumor worldwide. Tumor recurrence and metastasis contribute to the bad clinical outcome of HCC patients. Substantial studies have displayed lncRNAs modulate various tumorigenic processes of many cancers. Our current work was aimed to investigate the function of LINC00675 in HCC and to recognize the potential interactions between lncRNAs and microRNAs. GFI1 can exhibit a significant role in the progression of human malignant tumors. Firstly, GFI1 was identified using real-time PCR in HCC tissues and cells. In this work, we indicated GFI1 was remarkably reduced in HCC tissues and cells. Meanwhile, GFI1 specifically interacted with the promoter of LINC00675. Up-regulation of LINC00675 obviously repressed the migration and invasion capacity of SMCC-7721 and QGY-7703 cells . Moreover, decrease of LINC00675 competitively bound to miR-942-5p that contributed to the miRNA-mediated degradation of GFI1, thus facilitated HCC metastasis. The ceRNA function of LINC00675 in HCC cells was assessed and confirmed using RNA immunoprecipitation assay and RNA pull-down assays in our work. Additionally, we proved overexpression of miR-942-5p promoted HCC progression, which was reversed by the up-regulation of GFI1. In summary, LINC00675 might act as a prognostic marker for HCC, which can inhibit HCC development regulating miR-942-5p and GFI1.

摘要

肝细胞癌(HCC)是全球常见的恶性肝脏肿瘤。肿瘤复发和转移导致HCC患者临床预后不良。大量研究表明,长链非编码RNA(lncRNAs)可调节多种癌症的各种致癌过程。我们目前的工作旨在研究LINC00675在HCC中的功能,并识别lncRNAs与微小RNA(miRNAs)之间的潜在相互作用。生长因子独立1(GFI1)在人类恶性肿瘤进展中可发挥重要作用。首先,通过实时定量聚合酶链反应(PCR)在HCC组织和细胞中鉴定GFI1。在本研究中,我们发现HCC组织和细胞中GFI1显著降低。同时,GFI1与LINC00675的启动子特异性相互作用。LINC00675的上调明显抑制了SMCC - 7721和QGY - 7703细胞的迁移和侵袭能力。此外,LINC00675的减少竞争性结合miR - 942 - 5p,导致miRNA介导的GFI1降解,从而促进HCC转移。在我们的研究中,使用RNA免疫沉淀试验和RNA下拉试验评估并证实了LINC00675在HCC细胞中的竞争性内源RNA(ceRNA)功能。此外,我们证明miR - 942 - 5p的过表达促进HCC进展,而GFI1的上调可逆转这一过程。总之,LINC00675可能作为HCC的预后标志物,通过调节miR - 942 - 5p和GFI1来抑制HCC的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a31/7820889/bc23bf4a787d/fonc-10-607593-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a31/7820889/e8c2554375a6/fonc-10-607593-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a31/7820889/c25c9ffb4fdf/fonc-10-607593-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a31/7820889/bc23bf4a787d/fonc-10-607593-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a31/7820889/e8c2554375a6/fonc-10-607593-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a31/7820889/c25c9ffb4fdf/fonc-10-607593-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a31/7820889/bc23bf4a787d/fonc-10-607593-g007.jpg

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