LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p

Abstract While long noncoding RNAs (lncRNAs) have been reported to play an important role in human cancer types, they remain poorly understood in papillary thyroid carcinoma (PTC). The aim of this study was to use genome-wide expression profiling to identify lncRNAs acting as competing endogenous RN...

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Main Authors: Kai Guo, Kai Qian, Yuan Shi, Tuanqi Sun, Zhuoying Wang
Format: Article
Language:English
Published: Nature Publishing Group 2021-11-01
Series:Cell Death and Disease
Online Access:https://doi.org/10.1038/s41419-021-04386-0
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author Kai Guo
Kai Qian
Yuan Shi
Tuanqi Sun
Zhuoying Wang
author_facet Kai Guo
Kai Qian
Yuan Shi
Tuanqi Sun
Zhuoying Wang
author_sort Kai Guo
collection DOAJ
description Abstract While long noncoding RNAs (lncRNAs) have been reported to play an important role in human cancer types, they remain poorly understood in papillary thyroid carcinoma (PTC). The aim of this study was to use genome-wide expression profiling to identify lncRNAs acting as competing endogenous RNAs (ceRNAs) in PTC. We constructed a ceRNA network based on our lncRNA microarray data and validated the correlation between myocardial infarction-associated transcript lncRNA (MIAT), miRNA-150-5p, and EZH2 in vitro and in vivo. We found 15 lncRNAs, 28 miRNAs, and hundreds of mRNAs involved in this ceRNA network. Splendid positive correlations were found between the MIAT and EZH2 expression in types of cancer in TCGA data. Besides, significant differences in MIAT/EZH2 expression were found among various clinicopathological features. Gain- and loss-of-function experiments revealed that MIAT inhibited cell proliferation and migration in vitro. Moreover, EZH2 was identified as a direct downstream target of miR-150-5p in PTC cells. Restoration of EZH2 expression partially abolished the biological effects of miR-150-5p. Furthermore, overexpression of MIAT was inversely correlated with miR-150-5p expression. Knockdown of MIAT produced significant behavioral alter maybe partly due to the function of the MIAT-150-5p-EZH2 network. Our findings suggest MIAT may inhibit EZH2 expression and promote PTC cell invasion via the miR-150/EZH2 pathway. Therefore, MIAT may serve as a valuable prognostic biomarker and therapeutic target for PTC.
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spelling doaj.art-963ead95d85f47af9270bc53e8c138032022-12-21T19:27:14ZengNature Publishing GroupCell Death and Disease2041-48892021-11-01121211210.1038/s41419-021-04386-0LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5pKai Guo0Kai Qian1Yuan Shi2Tuanqi Sun3Zhuoying Wang4Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji HospitalDepartment of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji HospitalDepartment of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji HospitalDepartment of Head and Neck Surgery, Fudan University Shanghai Cancer CenterDepartment of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji HospitalAbstract While long noncoding RNAs (lncRNAs) have been reported to play an important role in human cancer types, they remain poorly understood in papillary thyroid carcinoma (PTC). The aim of this study was to use genome-wide expression profiling to identify lncRNAs acting as competing endogenous RNAs (ceRNAs) in PTC. We constructed a ceRNA network based on our lncRNA microarray data and validated the correlation between myocardial infarction-associated transcript lncRNA (MIAT), miRNA-150-5p, and EZH2 in vitro and in vivo. We found 15 lncRNAs, 28 miRNAs, and hundreds of mRNAs involved in this ceRNA network. Splendid positive correlations were found between the MIAT and EZH2 expression in types of cancer in TCGA data. Besides, significant differences in MIAT/EZH2 expression were found among various clinicopathological features. Gain- and loss-of-function experiments revealed that MIAT inhibited cell proliferation and migration in vitro. Moreover, EZH2 was identified as a direct downstream target of miR-150-5p in PTC cells. Restoration of EZH2 expression partially abolished the biological effects of miR-150-5p. Furthermore, overexpression of MIAT was inversely correlated with miR-150-5p expression. Knockdown of MIAT produced significant behavioral alter maybe partly due to the function of the MIAT-150-5p-EZH2 network. Our findings suggest MIAT may inhibit EZH2 expression and promote PTC cell invasion via the miR-150/EZH2 pathway. Therefore, MIAT may serve as a valuable prognostic biomarker and therapeutic target for PTC.https://doi.org/10.1038/s41419-021-04386-0
spellingShingle Kai Guo
Kai Qian
Yuan Shi
Tuanqi Sun
Zhuoying Wang
LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p
Cell Death and Disease
title LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p
title_full LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p
title_fullStr LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p
title_full_unstemmed LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p
title_short LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p
title_sort lncrna miat promotes thyroid cancer progression and function as cerna to target ezh2 by sponging mir 150 5p
url https://doi.org/10.1038/s41419-021-04386-0
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