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microRNA-569 通过直接靶向 NUSAP1 抑制胰腺癌中的肿瘤转移。

microRNA-569 inhibits tumor metastasis in pancreatic cancer by directly targeting NUSAP1.

机构信息

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China.

Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang 110001, China.

出版信息

Aging (Albany NY). 2022 Apr 28;14(8):3652-3665. doi: 10.18632/aging.204035.

DOI:10.18632/aging.204035
PMID:35483343
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9085231/
Abstract

MicroRNAs (miRNAs) are known to be involved in the development and progression of pancreatic cancer (PC). In this study, the prognostic significance and mechanistic role of microRNA-569 in PC were explored. Quantitative real-time PCR was used to detect the expression of microRNA-569 in PC tissues and cell lines. Scratch test and Transwell assay were conducted to detect migration and invasion ability. The xenograft nude mice model was used to determine tumor metastasis . The direct targets of microRNA-569 were determined by using bioinformatics analysis and a dual-luciferase reporter assay. The expression level of microRNA-569 was down-regulated in PC patients with a poor prognosis. and experiments indicated that over-expression of microRNA-569 inhibited the migration and invasion of PC cells. MicroRNA-569 negatively regulated NUSAP1 by directly binding its 3'-untranslated region. Further mechanism research implied that the ZEB1 pathway was involved in microRNA-569/NUSAP1 mediation of the biological behaviors in PC. These data demonstrated that microRNA-569 may exert a tumor-suppressing effect in PC and maybe a potential therapeutic target for PC patients.

摘要

微 RNA(miRNAs)已知参与胰腺癌(PC)的发展和进展。在这项研究中,探索了 microRNA-569 在 PC 中的预后意义和机制作用。采用实时定量 PCR 检测 PC 组织和细胞系中 microRNA-569 的表达。划痕试验和 Transwell 分析用于检测迁移和侵袭能力。利用异种移植裸鼠模型确定肿瘤转移。通过生物信息学分析和双荧光素酶报告基因实验确定 microRNA-569 的直接靶标。miRNA-569 在预后不良的 PC 患者中的表达水平下调。和实验表明,过表达 microRNA-569 抑制 PC 细胞的迁移和侵袭。miRNA-569 通过直接结合其 3'非翻译区负调控 NUSAP1。进一步的机制研究表明,ZEB1 通路参与了 microRNA-569/NUSAP1 介导的 PC 中的生物学行为。这些数据表明,microRNA-569 在 PC 中可能发挥肿瘤抑制作用,可能成为 PC 患者的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/3b90b0a6e8e4/aging-14-204035-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/c3e79325e438/aging-14-204035-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/ab358167e02b/aging-14-204035-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/378935d9defe/aging-14-204035-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/e5fddf6840f8/aging-14-204035-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/b58b838aa316/aging-14-204035-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/dcf0515f12f0/aging-14-204035-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/3b90b0a6e8e4/aging-14-204035-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/c3e79325e438/aging-14-204035-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/cfbcc1ebbcc5/aging-14-204035-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/ab358167e02b/aging-14-204035-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/378935d9defe/aging-14-204035-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/e5fddf6840f8/aging-14-204035-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/b58b838aa316/aging-14-204035-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/dcf0515f12f0/aging-14-204035-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b27/9085231/3b90b0a6e8e4/aging-14-204035-g008.jpg

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