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 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.

Noncoding RNAs in Thyroid-Follicular-Cell-Derived Carcinomas

“…Clearly, a multitude of lncRNAs are deregulated in TC and somehow functionally linked to its appearance and progression. To name a few, we can refer to the promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR) [151], SLC26A4 antisense RNA 1 (SLC26A4-AS1) [152], and myocardial infarction-associated transcript (MIAT) [153]. However, other reviews on the role of lncRNAs in TC were recently published (e.g., [154,155]).…”

Emerging role of lncRNAs in drug resistance mechanisms in head and neck squamous cell carcinoma

“…A similar effect has been observed in many other cancer types, with anti-apoptotic, pro-proliferative, and pro-migratory functions, along with the induction of EMT, activation of oncogenic signaling pathways, and changes in the tumor microenvironment, contributing to anti-cancer DR ( 165 ). Another well-studied lncRNA that promotes the proliferation, migration, and chemoresistance of several cancer types is the myocardial infarction-associated transcript (MIAT) ( 166 – 169 ). According to Zhu et al., an elevated MIAT level upregulates HMB1 expression, contributing to cisplatin resistance and poor clinical outcomes ( 121 ).…”

Long Noncoding RNA LINC00467: Role in Various Human Cancers

“…( Yan et al, 2022 ) Besides MIR17HG also inhibits non-small cell lung cancer via functioning as a ceRNA of miR-142-3p. ( Wei et al, 2020 ) Through this regulatory mode, lncRNAs are widely involved in the course of various diseases, including thyroid cancer ( Guo et al, 2021 ), renal fibrosis ( Tang et al, 2021 ), atherosclerotic plaques ( Ann et al, 2021 ), among others.…”