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      Long noncoding RNA NEAT1, regulated by LIN28B, promotes cell proliferation and migration through sponging miR-506 in high-grade serous ovarian cancer

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          Abstract

          The aberrant expression of long noncoding RNAs (lncRNAs) has been reported frequently in specific cancers, including high-grade serous ovarian cancer (HGSOC). The purpose of the present study was to explore the clinical significance and underlying mechanisms of a significantly dysregulated lncRNA (NEAT1) in HGSOC. Our results showed that elevated NEAT1 expression in human HGSOC specimens correlated with a poor prognosis. Functional experiments demonstrated that knockdown of NEAT1 significantly prohibited ovarian cancer cell proliferation and invasion in vitro and restrained tumor growth in vivo. LIN28B was identified by bioinformatics analysis along with experimental evidence as a direct actor that enhanced NEAT1 stability. A rescue functional assay confirmed that the LIN28B/NEAT1 axis contributed to oncogenic functions in ovarian cancer cells. Moreover, gene expression profile data and dual luciferase reporter assay results demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for miR-506 to promote cell proliferation and migration. Taken together, our results showed that NEAT1, stabilized by LIN28B, promoted HGSOC progression by sponging miR-506. Thus, NEAT1 can be regarded as a vital diagnostic biomarker for HGSOC and a therapeutic target.

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          Gene regulation in the immune system by long noncoding RNAs

          Long non-coding RNAs (lncRNAs) are being increasingly appreciated as important regulators of gene expression. Chang and colleagues review the roles identified for lncRNAs in the immune system and discuss models for how lncRNAs mediate their effects.
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            Lin28: primal regulator of growth and metabolism in stem cells.

            In recent years, the highly conserved Lin28 RNA-binding proteins have emerged as factors that define stemness in several tissue lineages. Lin28 proteins repress let-7 microRNAs and influence mRNA translation, thereby regulating the self-renewal of mammalian embryonic stem cells. Subsequent discoveries revealed that Lin28a and Lin28b are also important in organismal growth and metabolism, tissue development, somatic reprogramming, and cancer. In this review, we discuss the Lin28 pathway and its regulation, outline its roles in stem cells, tissue development, and pathogenesis, and examine the ramifications for re-engineering mammalian physiology. Copyright © 2013 Elsevier Inc. All rights reserved.
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              LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression.

              LIN28B regulates developmental processes by modulating microRNAs (miRNAs) of the let-7 family. A role for LIN28B in cancer has been proposed but has not been established in vivo. Here, we report that LIN28B showed genomic aberrations and extensive overexpression in high-risk neuroblastoma compared to several other tumor entities and normal tissues. High LIN28B expression was an independent risk factor for adverse outcome in neuroblastoma. LIN28B signaled through repression of the let-7 miRNAs and consequently resulted in elevated MYCN protein expression in neuroblastoma cells. LIN28B-let-7-MYCN signaling blocked differentiation of normal neuroblasts and neuroblastoma cells. These findings were fully recapitulated in a mouse model in which LIN28B expression in the sympathetic adrenergic lineage induced development of neuroblastomas marked by low let-7 miRNA levels and high MYCN protein expression. Interference with this pathway might offer therapeutic perspectives.
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                Author and article information

                Contributors
                wu.xh@fudan.edu.cn
                Journal
                Cell Death Dis
                Cell Death Dis
                Cell Death & Disease
                Nature Publishing Group UK (London )
                2041-4889
                28 August 2018
                28 August 2018
                September 2018
                : 9
                : 9
                : 861
                Affiliations
                [1 ]ISNI 0000 0004 1808 0942, GRID grid.452404.3, Department of Gynecologic Oncology, , Fudan University Shanghai Cancer Center, ; Shanghai, China
                [2 ]ISNI 0000 0001 0125 2443, GRID grid.8547.e, Department of Oncology, Shanghai Medical College, , Fudan University, ; Shanghai, China
                [3 ]ISNI 0000 0004 1808 0942, GRID grid.452404.3, Department of Pathology, , Fudan University Shanghai Cancer Center, ; Shanghai, China
                Article
                908
                10.1038/s41419-018-0908-z
                6113267
                30154460
                57835840-e920-4e69-a297-619e3de5d8ff
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 May 2018
                : 6 July 2018
                : 22 July 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81672569
                Award Recipient :
                Funded by: the Science and Technology Commission of Shanghai Municipality (15411962000;17411963000)
                Categories
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                © The Author(s) 2018

                Cell biology
                Cell biology

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