MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1

Osteosarcoma (OS) is the most common bone cancer worldwide. There is evidence that microRNA-409 (miR-409-3p) is involved in tumorigenesis and cancer progression, however, its possible role in OS requires clarification. In the present study, we evaluated the expression level, clinical significance, a...

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Main Authors: Liang Wu, Yiming Zhang, Zhongyue Huang, Huijie Gu, Kaifeng Zhou, Xiaofan Yin, Jun Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-02-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2019.00137/full
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spelling doaj-61104eed28a54966a7a5c2d338ac55ab2020-11-24T23:46:31ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-02-011010.3389/fphar.2019.00137432124MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1Liang WuYiming ZhangZhongyue HuangHuijie GuKaifeng ZhouXiaofan YinJun XuOsteosarcoma (OS) is the most common bone cancer worldwide. There is evidence that microRNA-409 (miR-409-3p) is involved in tumorigenesis and cancer progression, however, its possible role in OS requires clarification. In the present study, we evaluated the expression level, clinical significance, and mode of action of miR-409-3p in OS. The miR-409-3p levels were diminished in the OS cells and tissues compared with associated adjacent non-tumor tissues and a non-cancer osteoplastic cell line. Low miR-409-3p expression levels were associated with clinical stage and distant metastasis in patients with OS. Resumption of miR-409-3p expression attenuated OS cell proliferation and invasion. Additionally, based on informatics analyses, we predicted that zinc-finger E-box-binding homeobox-1 (ZEB1) is a possible target of miR-409-3p. This hypothesis was confirmed using luciferase reporter assays, reverse transcription-quantitative real-time polymerase chain reaction, and Western blot analyses. The findings of the current study indicated that ZEB1 was up-regulated in the OS tissues and cell lines, and that this up-regulation was inversely proportional to miR-409-3p expression levels. Furthermore, down-regulation of ZEB1 decreased OS cell invasion and proliferation, illustrating that the tumor suppressive role of miR-409-3p in OS cells may be exerted via negative regulation of ZEB1. Taken together, our observations highlight the potential role of miR-409-3p as a tumor suppressor in OS partially through down-regulation of ZEB1 and suggest that miR-409-3p has potential applications in OS treatment.https://www.frontiersin.org/article/10.3389/fphar.2019.00137/fullosteosarcomamicroRNA-409molecular mechanismzinc-finger E-box-binding homeobox-1invasion
collection DOAJ
language English
format Article
sources DOAJ
author Liang Wu
Yiming Zhang
Zhongyue Huang
Huijie Gu
Kaifeng Zhou
Xiaofan Yin
Jun Xu
spellingShingle Liang Wu
Yiming Zhang
Zhongyue Huang
Huijie Gu
Kaifeng Zhou
Xiaofan Yin
Jun Xu
MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1
Frontiers in Pharmacology
osteosarcoma
microRNA-409
molecular mechanism
zinc-finger E-box-binding homeobox-1
invasion
author_facet Liang Wu
Yiming Zhang
Zhongyue Huang
Huijie Gu
Kaifeng Zhou
Xiaofan Yin
Jun Xu
author_sort Liang Wu
title MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1
title_short MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1
title_full MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1
title_fullStr MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1
title_full_unstemmed MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1
title_sort mir-409-3p inhibits cell proliferation and invasion of osteosarcoma by targeting zinc-finger e-box-binding homeobox-1
publisher Frontiers Media S.A.
series Frontiers in Pharmacology
issn 1663-9812
publishDate 2019-02-01
description Osteosarcoma (OS) is the most common bone cancer worldwide. There is evidence that microRNA-409 (miR-409-3p) is involved in tumorigenesis and cancer progression, however, its possible role in OS requires clarification. In the present study, we evaluated the expression level, clinical significance, and mode of action of miR-409-3p in OS. The miR-409-3p levels were diminished in the OS cells and tissues compared with associated adjacent non-tumor tissues and a non-cancer osteoplastic cell line. Low miR-409-3p expression levels were associated with clinical stage and distant metastasis in patients with OS. Resumption of miR-409-3p expression attenuated OS cell proliferation and invasion. Additionally, based on informatics analyses, we predicted that zinc-finger E-box-binding homeobox-1 (ZEB1) is a possible target of miR-409-3p. This hypothesis was confirmed using luciferase reporter assays, reverse transcription-quantitative real-time polymerase chain reaction, and Western blot analyses. The findings of the current study indicated that ZEB1 was up-regulated in the OS tissues and cell lines, and that this up-regulation was inversely proportional to miR-409-3p expression levels. Furthermore, down-regulation of ZEB1 decreased OS cell invasion and proliferation, illustrating that the tumor suppressive role of miR-409-3p in OS cells may be exerted via negative regulation of ZEB1. Taken together, our observations highlight the potential role of miR-409-3p as a tumor suppressor in OS partially through down-regulation of ZEB1 and suggest that miR-409-3p has potential applications in OS treatment.
topic osteosarcoma
microRNA-409
molecular mechanism
zinc-finger E-box-binding homeobox-1
invasion
url https://www.frontiersin.org/article/10.3389/fphar.2019.00137/full
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