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Frontiers in Biology

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ISSN 1674-7992(Online)

CN 11-5892/Q

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Front. Biol.    2016, Vol. 11 Issue (6) : 413-426    https://doi.org/10.1007/s11515-016-1433-z
REVIEW
Cellular, physiological and pathological aspects of the long non-coding RNA NEAT1
Pang-Kuo Lo,Benjamin Wolfson,Qun Zhou()
Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
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Abstract

BACKGROUND: The majority of mammalian genomes have been found to be transcribed into non-coding RNAs. One category of non-coding RNAs is classified as long non-coding RNAs (lncRNAs) based on their transcript sizes larger than 200 nucleotides. Growing evidence has shown that lncRNAs are not junk transcripts and play regulatory roles in multiple aspects of biological processes. Dysregulation of lncRNA expression has also been linked to diseases, in particular cancer. Therefore, studies of lncRNAs have attracted significant interest in the field of medical research. Nuclear enriched abundant transcript 1 (NEAT1), a nuclear lncRNA, has recently emerged as a key regulator involved in various cellular processes, physiological responses, developmental processes, and disease development and progression.

OBJECTIVE: This review will summarize and discuss the most recent findings with regard to the roles of NEAT1 in the function of the nuclear paraspeckle, cellular pathways, and physiological responses and processes. Particularly, the most recently reported studies regarding the pathological roles of deregulated NEAT1 in cancer are highlighted in this review.

METHODS: We performed a systematic literature search using the Pubmed search engine. Studies published over the past 8 years (between January 2009 and August 2016) were the sources of literature review. The following keywords were used: “Nuclear enriched abundant transcript 1,” “NEAT1,” and “paraspeckles.”

RESULTS: The Pubmed search identified 34 articles related to the topic of the review. Among the identified literature, 13 articles report findings related to cellular functions of NEAT1 and eight articles are the investigations of physiological functions of NEAT1. The remaining 13 articles are studies of the roles of NEAT1 in cancers.

CONCLUSION: Recent advances in NEAT1 studies reveal the multifunctional roles of NEAT1 in various biological processes, which are beyond its role in nuclear paraspeckles. Recent studies also indicate that dysregulation of NEAT1 function contributes to the development and progression of various cancers. More investigations will be needed to address the detailed mechanisms regarding how NEAT1 executes its cellular and physiological functions and how NEAT1 dysregulation results in tumorigenesis, and to explore the potential of NEAT1 as a target in cancer diagnosis, prognosis and therapy.
Keywords long non-coding RNAs (lncRNAs)      nuclear enriched abundant transcript 1 (NEAT1)      paraspeckles      microRNAs (miRNAs)      epigenetic regulation      cancer     
Corresponding Author(s): Qun Zhou   
Just Accepted Date: 14 November 2016   Online First Date: 08 December 2016    Issue Date: 26 December 2016
 Cite this article:   
Pang-Kuo Lo,Benjamin Wolfson,Qun Zhou. Cellular, physiological and pathological aspects of the long non-coding RNA NEAT1[J]. Front. Biol., 2016, 11(6): 413-426.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-016-1433-z
https://academic.hep.com.cn/fib/EN/Y2016/V11/I6/413
Fig.1  The hypothetical model for paraspeckle formation in the cell nucleus. The human NEAT1 gene is transcribed into two lncRNA isoform transcripts, NEAT1_1 and NEAT1_2. Only the NEAT1_1 transcript is polyadenylated. The assembly of paraspeckles mainly involves the two steps of component recruitment. In the first recruitment, two abundant paraspeckle proteins, p54nrb and PSF, bind to the internal region of the NEAT1_2 transcript. The first recruitment triggers the second recruitment of PSPC1, NEAT1_1 and other paraspeckle proteins (PSPs) to form paraspeckles.
Fig.2  The regulation and function of NEAT1 in the cell. NEAT1 expression is upregulated by hypoxia and DNA damage stress via activation of upstream transcription factors HIF-2 and p53, respectively. microRNAs (listed in Table 1) are involved in positively and negatively regulating NEAT1 expression. BRCA1 is also found to negatively regulate NEAT1 expression. NEAT1 is overexpressed during tumorigenesis of various types of tissue through dysregulation of the aforementioned signaling pathways, microRNA expression and other unknown mechanisms. NEAT1 executes its functions through acting as an architectural RNA for paraspeckle assembly and as a sponge RNA for inhibiting microRNAs, and through interacting with chromatin for epigenetic regulation of gene expression.
Regulatory mechanism microRNA microRNA target Interaction mechanism Dysregulation in cancer Reference
As a sponge for microRNAs miR-98-5p CTR1 NEAT1 inhibits miR-98-5p to induce CTR1 expression, resulting in increased chemosensitivity. NSCLC (Lung cancer) Jiang et al., 2016
miR-107 CDK6 NEAT1 inhibits miR-107 to induce CDK6 expression, which promotes cell growth. LSCC (Head and neck cancer) Wang et al., 2016
miR-204 ZEB1 NEAT1 inhibits miR-204 to induce ZEB1 expression, leading to EMT activation. NPC (Head and neck cancer) Lu, et al., 2016
miR-449b-5p c-Met NEAT1 inhibits miR-449b-5p to induce c-Met expression. Brain cancer Zhen et al., 2016
Epigenetic regulation of microRNAs miR-129-5p WNT4 NEAT1 silences miR-129-5p expression via increasing DNA methylation of miR-129 gene. Breast cancer Lo et al., 2016
Regulated by microRNAs miR-124-3p NEAT1 miR-124-3p inhibits NEAT1 expression. Ovarian cancer Chai et al., 2016
miR-140 NEAT1 miR-140 stabilizes NEAT1 and increase its expression. This regulation is required for adipogenesis Gernapudi et al., 2016
miR-449a NEAT1 miR-449a suppresses NEAT1 expression. Lung cancer You et al., 2014
miR-548ar-3p NEAT1 miR-548ar-3p decreases NEAT1 expression. Breast cancer Ke et al., 2016
Tab.1  The regulatory interactions between the lncRNA NEAT1 and microRNAs
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