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.
Highlights
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy and has a rapidly increasing global incidence rate [1]
The competing endogenous RNA hypothesis has attracted more attention [7,8,9]. This hypothesis describes a complex post-transcriptional regulatory network mediated by microRNAs: by sharing one or more miRNA response elements (MREs), protein-coding, and long noncoding RNAs compete for binding to miRNAs and functionally liberate mRNA regulated by the miRNAs
Through the competing endogenous RNAs (ceRNAs) network, we found there may be a correlation among myocardial infarction-associated transcript lncRNA (MIAT), miR-150-5p, and six mRNAs including LDLR, SMC3, EZH2, SAR1A, PERP, and MTCH2 (Fig. 3B)
Summary
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy and has a rapidly increasing global incidence rate [1]. The competing endogenous RNA (ceRNA) hypothesis has attracted more attention [7,8,9]. This hypothesis describes a complex post-transcriptional regulatory network mediated by microRNAs (miRNAs): by sharing one or more miRNA response elements (MREs), protein-coding, and long noncoding RNAs (lncRNAs) compete for binding to miRNAs and functionally liberate mRNA regulated by the miRNAs. to understand the function of ceRNA networks in the pathogenesis and pathological conditions of PTC, further research is required
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