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长链非编码 RNA LOXL1-AS1 通过调节 ABCA1 作为 miR-324-3p 的 ceRNA 促进胆管癌进展。

Long non-coding RNA LOXL1-AS1 acts as a ceRNA for miR-324-3p to contribute to cholangiocarcinoma progression via modulation of ATP-binding cassette transporter A1.

机构信息

Department of General Medicine, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China.

Department of Food and Drug Control, Qiqihar Institute for Food and Drug Control, Qiqihar, 161000, China.

出版信息

Biochem Biophys Res Commun. 2019 Jun 11;513(4):827-833. doi: 10.1016/j.bbrc.2019.04.089. Epub 2019 Apr 16.

Abstract

Accumulating evidence has appreciated long non-coding RNAs (lncRNAs) as novel prognostic markers and therapeutic targets in malignant carcinomas. Here, we aim to investigate the value of a novel cancer-related lncRNA, LOXL1-AS1, in cholangiocarcinoma (CCA). LOXL1-AS1 was found overexpressed in CCA tissues screened by high-throughput sequencing technology. Upregulation of LOXL1-AS1 was identified by TCGA database and qRT-PCR analysis. Additionally, upregulation of LOXL1-AS1 was associated with lymph node invasion, advanced TNM stages and unfavorable prognosis. Loss-of-function and gain-of-function experiments were conducted and validated that LOXL1-AS1 could facilitate cell proliferation, migration and invasion and attenuate cell apoptosis. Moreover, luciferase reporter and rescue assays indicated that LOXL1-AS1 functioned as a ceRNA to elevate ATP-binding cassette transporter A1 (ABCA1) level by sponging miR-324-3p and exhibited the malignant phenotypes of CCA cells, thereby playing an oncogenic role in CCA. Taken together, this study reveals that LOXL1-AS1 might act as a potential biomarker and therapeutic target for CCA clinical application.

摘要

越来越多的证据表明,长链非编码 RNA(lncRNA)可作为恶性肿瘤的新型预后标志物和治疗靶点。在这里,我们旨在研究一种新型与癌症相关的 lncRNA,即 LOXL1-AS1,在胆管癌(CCA)中的价值。通过高通量测序技术筛选出 CCA 组织中 LOXL1-AS1 过表达。TCGA 数据库和 qRT-PCR 分析鉴定 LOXL1-AS1 上调。此外,LOXL1-AS1 的上调与淋巴结浸润、晚期 TNM 分期和预后不良有关。通过功能丧失和功能获得实验验证,LOXL1-AS1 可促进细胞增殖、迁移和侵袭,并抑制细胞凋亡。此外,荧光素酶报告和挽救实验表明,LOXL1-AS1 可作为 ceRNA 通过海绵吸附 miR-324-3p 来升高 ABCA1 水平,并表现出 CCA 细胞的恶性表型,从而在 CCA 中发挥致癌作用。综上所述,本研究表明 LOXL1-AS1 可能作为 CCA 临床应用的潜在生物标志物和治疗靶点。

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