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微小RNA-26a通过直接靶向高迁移率族蛋白A1抑制骨肉瘤的迁移和侵袭。

miR-26a suppresses osteosarcoma migration and invasion by directly targeting HMGA1.

作者信息

Liu Jianyong, Mi Bo, Wang Yi, Shi Chunling, Mi Xiufang, Lu Yingying, Yu Peilin

机构信息

Department of Orthopedics, People's Hospital of Weifang, Weifang, Shandong 261000, P.R. China.

Department of Medicine, The First People's Hospital of Jinan, Jinan, Shandong 250000, P.R. China.

出版信息

Oncol Lett. 2018 Jun;15(6):8303-8310. doi: 10.3892/ol.2018.8359. Epub 2018 Mar 28.

Abstract

Osteosarcoma (OS) is identified as the most commonly diagnosed malignant cancer of bone, and has approximately three million new cases annually. miR-26a plays an important role in the development of various types of cancer. We investigated whether miR-26a can regulate the migration and invasion of OS by targeting high-mobility group A1 HMGA1. Western blot analysis was used to identify the changes of protein levels. Reverse transcription-quantitative PCR was used to test expression levels of genes and miR-26a. Luciferase reporter assay was used to test the specific target gene of miR-26a. Transwell assay was employed to determine the migration and invasion of OS cell lines. In the present study, miRNA-26a was frequently downregulated in OS tissues and cells. Overexpression of miR-26a inhibited cell migration and invasion . In addition, miR-26a downregulated HMGA1 by targeting its 3'-UTR and knockdown of HMGA1 significantly suppressed the migration and invasion of two osteosarcoma cell lines . miR-26a suppressed the migration and invasion of OS cells by targeting HMGA1, suggesting that miR-26a/HMGA1 axis provides a new prospective therapeutic strategy for OS.

摘要

骨肉瘤(OS)是最常见的骨恶性肿瘤,每年新增病例约300万。miR-26a在各类癌症的发展过程中发挥着重要作用。我们研究了miR-26a是否可通过靶向高迁移率族蛋白A1(HMGA1)来调控骨肉瘤的迁移和侵袭。采用蛋白质印迹分析来鉴定蛋白质水平的变化。运用逆转录定量聚合酶链反应检测基因和miR-26a的表达水平。采用荧光素酶报告基因检测法检测miR-26a的特异性靶基因。使用Transwell实验来测定骨肉瘤细胞系的迁移和侵袭能力。在本研究中,miRNA-26a在骨肉瘤组织和细胞中经常下调。miR-26a的过表达抑制细胞迁移和侵袭。此外,miR-26a通过靶向HMGA1的3'-非翻译区下调HMGA1,敲低HMGA1可显著抑制两种骨肉瘤细胞系的迁移和侵袭。miR-26a通过靶向HMGA1抑制骨肉瘤细胞迁移和侵袭,提示miR-26a/HMGA1轴为骨肉瘤提供了一种新的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5ff/6004719/9a18e58ccc98/ol-15-06-8303-g00.jpg

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