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PMID: 34811354 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

Cell death & disease ·Vol. 12 ·No. 12 ·2021-00-22 ·Pages 1097

Guo K, Qian K, Shi Y, Sun T, Wang Z

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.

MeSH Terms
Animals Biomarkers, Tumor/metabolism Cell Proliferation/physiology Disease Progression Enhancer of Zeste Homolog 2 Protein/metabolism Female Heterografts Humans Mice Mice, Inbred BALB C MicroRNAs/genetics,metabolism RNA, Long Noncoding/genetics,metabolism Thyroid Neoplasms/genetics,metabolism,pathology Transfection
Chemicals
Biomarkers, Tumor Enhancer of Zeste Homolog 2 Protein MicroRNAs RNA, Long Noncoding MIR150, human Miat long non-coding RNA EZH2 protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Guo Kai
Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, 200001, Shanghai, China.
Qian Kai
Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, 200001, Shanghai, China.
Shi Yuan
Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, 200001, Shanghai, China.
Sun Tuanqi
Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. | Department of Oncology, Fudan University Shanghai Medical College, 200032, Shanghai, China.
Wang Zhuoying ORCID
Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, 200001, Shanghai, China. zhuoyingwang@hotmail.com.
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Article Info
Journal
Cell death & disease
Abbr.
Cell Death Dis
ISSN
2041-4889
DOI
10.1038/s41419-021-04386-0
Email
zhuoyingwang@hotmail.com
Published
2021-00-22
Epub
2021-00-22
Pages
1097
Language
English
Region
England
NLM ID
101524092
PMCID
PMC8608816
Subset
IM
External Links
PubMed source DOI: 10.1038/s41419-021-04386-0 PMC Full Text View journal details
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