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长链非编码RNA HOTTIP通过与c-Myc形成正反馈环促进骨肉瘤细胞的迁移、侵袭和上皮-间质转化。

lncRNA HOTTIP facilitates osteosarcoma cell migration, invasion and epithelial-mesenchymal transition by forming a positive feedback loop with c-Myc.

作者信息

Tang Yang, Ji Fang

机构信息

Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200438, P.R. China.

出版信息

Oncol Lett. 2019 Aug;18(2):1649-1656. doi: 10.3892/ol.2019.10463. Epub 2019 Jun 10.

DOI:10.3892/ol.2019.10463
PMID:31423232
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6607149/
Abstract

Homeobox A transcript at the distal tip (HOTTIP) is an oncogenic long non-coding RNA in cancer. The aim of the present study was to investigate the function and mechanism of HOTTIP in the aggressive behaviors of human osteosarcoma (OS) cells. Expression levels of HOTTIP and epithelial-mesenchymal transition (EMT) markers were determined by reverse transcription-quantitative PCR. Cell invasive and migratory abilities were evaluated using Matrigel and wound healing assays, respectively. Knockdown of HOTTIP expression was achieved by small interfering RNA-mediated silencing. Overexpression of c-Myc was accomplished by transfecting cultured cells with a c-Myc overexpression plasmid. HOTTIP was demonstrated to be upregulated in OS tissues and cell lines; knockdown of HOTTIP inhibited OS cell migration, invasion and EMT, and suppressed c-Myc expression. In addition, overexpression of c-Myc increased HOTTIP expression and enhanced OS cell migration and invasion. HOTTIP promoted cell migration and invasion by upregulating c-Myc in OS. The positive feedback loop formed by HOTTIP and c-Myc may contribute to OS progression, and HOTTIP may act as a therapeutic target for OS.

摘要

远端同源盒A转录本（HOTTIP）是癌症中的一种致癌长链非编码RNA。本研究旨在探讨HOTTIP在人骨肉瘤（OS）细胞侵袭性行为中的功能及机制。通过逆转录定量PCR测定HOTTIP和上皮-间质转化（EMT）标志物的表达水平。分别采用基质胶和伤口愈合实验评估细胞的侵袭和迁移能力。通过小分子干扰RNA介导的沉默实现HOTTIP表达的敲低。通过用c-Myc过表达质粒转染培养细胞来实现c-Myc的过表达。结果表明，HOTTIP在OS组织和细胞系中上调；敲低HOTTIP可抑制OS细胞迁移、侵袭和EMT，并抑制c-Myc表达。此外，c-Myc的过表达增加了HOTTIP的表达，并增强了OS细胞的迁移和侵袭能力。HOTTIP通过上调OS中的c-Myc促进细胞迁移和侵袭。由HOTTIP和c-Myc形成的正反馈环可能促进OS进展，并且HOTTIP可能作为OS的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/5b5b7bcdf4f8/ol-18-02-1649-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/4b83d8fa40bc/ol-18-02-1649-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/2b068c53b27a/ol-18-02-1649-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/1512a7743c77/ol-18-02-1649-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/2bf2696ecbef/ol-18-02-1649-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/598303ecaaed/ol-18-02-1649-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/5b5b7bcdf4f8/ol-18-02-1649-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/4b83d8fa40bc/ol-18-02-1649-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/2b068c53b27a/ol-18-02-1649-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/1512a7743c77/ol-18-02-1649-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/2bf2696ecbef/ol-18-02-1649-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/598303ecaaed/ol-18-02-1649-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d44/6607149/5b5b7bcdf4f8/ol-18-02-1649-g05.jpg

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本文引用的文献

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LncRNA TP73-AS1 predicts poor prognosis and functions as oncogenic lncRNA in osteosarcoma.长链非编码RNA TP73-AS1预测骨肉瘤预后不良并作为致癌长链非编码RNA发挥作用。
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Long Non-coding RNA Structure and Function: Is There a Link?长链非编码RNA的结构与功能：它们之间有关联吗？
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