Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1

The epithelial-mesenchymal transition (EMT) is a vital step in osteosarcoma (OS) progression toward metastasis, but the specific molecular events governing this process are incompletely characterized, with miRNAs having increasingly been found to regulate the EMT. In this study, We assessed levels o...

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Main Authors: Shu-tao Zhu, Xiao Wang, Jun-yi Wang, Guang-hui Xi, Yang Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-04-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2020.00406/full
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author Shu-tao Zhu
Xiao Wang
Jun-yi Wang
Guang-hui Xi
Yang Liu
author_facet Shu-tao Zhu
Xiao Wang
Jun-yi Wang
Guang-hui Xi
Yang Liu
author_sort Shu-tao Zhu
collection DOAJ
description The epithelial-mesenchymal transition (EMT) is a vital step in osteosarcoma (OS) progression toward metastasis, but the specific molecular events governing this process are incompletely characterized, with miRNAs having increasingly been found to regulate the EMT. In this study, We assessed levels of miR-22 and its target, Twist1, via real-time PCR (qRT-PCR). We further used functional proliferation assays, measures of cell morphology, and western blotting to assess the functional relevance of miR-22 in OS and confirmed Twist1 as a miR-22 target via luciferase reporter assay. We observed a significant decrease in miR-22 levels in OS tumor samples relative to normal tissue, with such downregulating being significantly associated with tumor histological grade. When overexpressed, miR-22 impaired OS cell proliferation and EMT progression. We found Twist1 to be a direct miR-22 target, with levels of miR-22 and Twist1 mRNA being inversely correlated in patient samples. When overexpressed, miR-22 suppressed Twist1 translation and thereby attenuated the EMT in OS cells. These results clearly demonstrate that miR-22 can regulate the EMT in OS cells via targeting Twist1, thus highlighting a potentially novel pathway that can be therapeutically targeted in order to treat OS.
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spelling doaj.art-826afdc9661f42638270b7d2a3c6f6cc2022-12-21T18:14:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-04-011010.3389/fonc.2020.00406504570Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1Shu-tao ZhuXiao WangJun-yi WangGuang-hui XiYang LiuThe epithelial-mesenchymal transition (EMT) is a vital step in osteosarcoma (OS) progression toward metastasis, but the specific molecular events governing this process are incompletely characterized, with miRNAs having increasingly been found to regulate the EMT. In this study, We assessed levels of miR-22 and its target, Twist1, via real-time PCR (qRT-PCR). We further used functional proliferation assays, measures of cell morphology, and western blotting to assess the functional relevance of miR-22 in OS and confirmed Twist1 as a miR-22 target via luciferase reporter assay. We observed a significant decrease in miR-22 levels in OS tumor samples relative to normal tissue, with such downregulating being significantly associated with tumor histological grade. When overexpressed, miR-22 impaired OS cell proliferation and EMT progression. We found Twist1 to be a direct miR-22 target, with levels of miR-22 and Twist1 mRNA being inversely correlated in patient samples. When overexpressed, miR-22 suppressed Twist1 translation and thereby attenuated the EMT in OS cells. These results clearly demonstrate that miR-22 can regulate the EMT in OS cells via targeting Twist1, thus highlighting a potentially novel pathway that can be therapeutically targeted in order to treat OS.https://www.frontiersin.org/article/10.3389/fonc.2020.00406/fullmiR-22EMTmetastasistwist1osteosarcoma
spellingShingle Shu-tao Zhu
Xiao Wang
Jun-yi Wang
Guang-hui Xi
Yang Liu
Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1
Frontiers in Oncology
miR-22
EMT
metastasis
twist1
osteosarcoma
title Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1
title_full Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1
title_fullStr Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1
title_full_unstemmed Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1
title_short Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1
title_sort downregulation of mir 22 contributes to epithelial mesenchymal transition in osteosarcoma by targeting twist1
topic miR-22
EMT
metastasis
twist1
osteosarcoma
url https://www.frontiersin.org/article/10.3389/fonc.2020.00406/full
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AT xiaowang downregulationofmir22contributestoepithelialmesenchymaltransitioninosteosarcomabytargetingtwist1
AT junyiwang downregulationofmir22contributestoepithelialmesenchymaltransitioninosteosarcomabytargetingtwist1
AT guanghuixi downregulationofmir22contributestoepithelialmesenchymaltransitioninosteosarcomabytargetingtwist1
AT yangliu downregulationofmir22contributestoepithelialmesenchymaltransitioninosteosarcomabytargetingtwist1