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NEAT1_2 functions as a competing endogenous RNA to regulate ATAD2 expression by sponging microRNA-106b-5p in papillary thyroid cancer.

ABSTRACT: Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA (lncRNA), is a core structural component of paraspeckles and is essential for paraspeckle formation. NEAT1 comprises two different isoforms: NEAT1_1 (3.7?kb) and NEAT1_2 (23?kb). Recently, NEAT1 has been shown to have oncogenic roles and to facilitate tumorigenesis in various human cancers. However, the function of NEAT1 in papillary thyroid cancer (PTC) is not well understood. The relative expression levels of NEAT1_2, ATPase family AAA domain-containing protein 2 (ATAD2), and microRNA-106b-5p (miR-106b-5p) were assessed via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Four PTC cell lines were used to detect the relative expression of NEAT1_2. The effects of NEAT1_2 on PTC cells were studied by RNA interference approaches in vitro. The effects of NEAT1_2 on downstream proteins were detected by western blotting. The underlying mechanism was clarified by a rescue experiment, and three dual-luciferase reporter assays. NEAT1_2 expression was markedly increased in PTC tissues and the PTC cell lines (K1 and TPC1). The relative expression level of NEAT1_2 was positively associated with TNM stage and tumor size. NEAT1_2 knockdown led to a significant inhibition of growth and metastasis, and induced apoptosis in PTC cells. Knockdown of NEAT1_2 significantly inhibited malignant biological behavior by downregulating the oncogene ATAD2. In addition, NEAT1_2 could act as a competing endogenous RNA to regulate the expression of ATAD2 through downregulating miR-106b-5p. Taken together, our results indicated that NEAT1_2 is overexpressed in PTC. NEAT1_2 could function as a competing endogenous RNA to regulate ATAD2 expression by sponging miR-106b-5p in PTC. Targeting NEAT1_2 could be a promising therapeutic strategy for patients with PTC.

SUBMITTER: Sun W

PROVIDER: S-EPMC5841310 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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NEAT1_2 functions as a competing endogenous RNA to regulate ATAD2 expression by sponging microRNA-106b-5p in papillary thyroid cancer.

Sun Wei W Lan Xiabin X Zhang Hao H Wang Zhihong Z Dong Wenwu W He Liang L Zhang Ting T Zhang Ping P Liu Jinhao J Qin Yuan Y

Cell death & disease 20180307 3

Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA (lncRNA), is a core structural component of paraspeckles and is essential for paraspeckle formation. NEAT1 comprises two different isoforms: NEAT1_1 (3.7 kb) and NEAT1_2 (23 kb). Recently, NEAT1 has been shown to have oncogenic roles and to facilitate tumorigenesis in various human cancers. However, the function of NEAT1 in papillary thyroid cancer (PTC) is not well understood. The relative expression levels of NEAT1_2, ATP ...[more]

PMID: 29515109

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Project description:The present study aimed to screen all types of RNAs involved in the development of papillary thyroid carcinoma (PTC). RNA‑sequencing data of PTC and normal samples were used for screening differentially expressed (DE) microRNAs (DE‑miRNAs), long non‑coding RNAs (DE‑lncRNAs) and genes (DEGs). Subsequently, lncRNA‑miRNA, miRNA‑gene (that is, miRNA‑mRNA) and gene‑gene interaction pairs were extracted and used to construct regulatory networks. Feature genes in the miRNA‑mRNA network were identified by topological analysis and recursive feature elimination analysis. A support vector machine (SVM) classifier was built using 15 feature genes, and its classification effect was validated using two microarray data sets that were downloaded from the Gene Expression Omnibus (GEO) database. In addition, Gene Ontology function and Kyoto Encyclopedia Genes and Genomes pathway enrichment analyses were conducted for genes identified in the ceRNA network. A total of 506 samples, including 447 tumor samples and 59 normal samples, were obtained from The Cancer Genome Atlas (TCGA); 16 DE‑lncRNAs, 917 DEGs and 30 DE‑miRNAs were screened. The miRNA‑mRNA regulatory network comprised 353 nodes and 577 interactions. From these data, 15 feature genes with high predictive precision (>95%) were extracted from the network and were used to form an SVM classifier with an accuracy of 96.05% (486/506) for PTC samples downloaded from TCGA, and accuracies of 96.81 and 98.46% for GEO downloaded data sets. The ceRNA regulatory network comprised 596 lines (or interactions) and 365 nodes. Genes in the ceRNA network were significantly enriched in 'neuron development', 'differentiation', 'neuroactive ligand‑receptor interaction', 'metabolism of xenobiotics by cytochrome P450', 'drug metabolism' and 'cytokine‑cytokine receptor interaction' pathways. Hox transcript antisense RNA, miRNA‑206 and kallikrein‑related peptidase 10 were nodes in the ceRNA regulatory network of the selected feature gene, and they may serve import roles in the development of PTC.

Dataset Information

NEAT1_2 functions as a competing endogenous RNA to regulate ATAD2 expression by sponging microRNA-106b-5p in papillary thyroid cancer.

Publications

NEAT1_2 functions as a competing endogenous RNA to regulate ATAD2 expression by sponging microRNA-106b-5p in papillary thyroid cancer.

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