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      LncRNA SNHG3 promotes bladder cancer proliferation and metastasis through miR‐515‐5p/GINS2 axis

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          Abstract

          Growing evidence suggests that long non‐coding RNAs (lncRNAs) are associated with carcinogenesis. LncRNA small nucleolar RNA host gene 3 (SNHG3) is up‐regulated in various cancers and positively associated with poor prognosis of these cancers. However, the precise role of lncRNA SNHG3 in bladder cancer (Bca) remains unclear. In our research, we first reported that lncRNA SNHG3 was up‐regulated in bladder cancer tissues and positively related to poor clinical prognosis. Moreover, knockdown of lncRNA SNHG3 significantly suppressed the proliferation, migration, invasion and EMT process of Bca cells in vitro and vivo. Mechanistically, we revealed that suppression of SNHG3 evidently enhanced miR‐515‐5p expression and decreased GINS2 expression at posttranscriptional levels. Moreover, SNHG3 positively regulated GINS2 expression by sponging miR‐515‐5p under a competing endogenous RNA (ceRNA) mechanism. To sum up, our study suggested lncRNA SNHG3 acted as a microRNA sponge and an oncogenic role in the progression of bladder cancer.

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          Most cited references27

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          Long noncoding RNA as modular scaffold of histone modification complexes.

          Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
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            Lnc RNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR‐20a‐5p/ HMGA 2 axis in breast cancer

            Abstract To study the regulatory effect of lncRNA HOTAIR/miR‐20a‐5p/ HMGA2 axis on breast cancer (BC) cell growth, cell mobility, invasiveness, and apoptosis. The microarray data of lncRNAs and mRNAs with differential expression in BC tissues were analyzed in the Cancer Genome Atlas (TCGA) database. LncRNA HOX transcript antisense RNA (lncRNA HOTAIR) expression in BC was assessed by qRT‐PCR. Cell viability was confirmed using MTT and colony formation assay. Cell apoptosis was analyzed by TdT‐mediated dUTP nick‐end labeling (TUNEL) assay. Cell mobility and invasiveness were testified by transwell assay. RNA pull‐down and dual luciferase assay were used for analysis of the correlation between lncRNA HOTAIR and miR‐20a‐5p, as well as relationship of miR‐20a‐5p with high mobility group AT‐hook 2 ( HMGA2). Tumor xenograft study was applied to confirm the correlation of lncRNA HOTAIR/miR‐20a‐5p/ HMGA2 axis on BC development in vivo. The expression levels of the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis. MiR‐20a‐5p was a target of lncRNA HOTAIR and had a negative correlation with lncRNA HOTAIR. MiR‐20a‐5p overexpression in BC suppressed cell growth, mobility, and invasiveness and facilitated apoptosis. HMGA2 was a target of miR‐20a‐5p, which significantly induced carcinogenesis of BC. BC cells progression was mediated by lncRNA HOTAIR via affecting miR‐20a‐5p/ HMGA2 in vivo. LncRNA HOTAIR affected cell growth, metastasis, and apoptosis via the miR‐20a‐5p/ HMGA2 axis in breast cancer.
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              Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA.

              Ezh2 functions as a histone H3 Lys 27 (H3K27) methyltransferase when comprising the Polycomb-Repressive Complex 2 (PRC2). Trimethylation of H3K27 (H3K27me3) correlates with transcriptionally repressed chromatin. The means by which PRC2 targets specific chromatin regions is currently unclear, but noncoding RNAs (ncRNAs) have been shown to interact with PRC2 and may facilitate its recruitment to some target genes. Here we show that Ezh2 interacts with HOTAIR and Xist. Ezh2 is phosphorylated by cyclin-dependent kinase 1 (CDK1) at threonine residues 345 and 487 in a cell cycle-dependent manner. A phospho-mimic at residue 345 increased HOTAIR ncRNA binding to Ezh2, while the phospho-mimic at residue 487 was ineffectual. An Ezh2 domain comprising T345 was found to be important for binding to HOTAIR and the 5' end of Xist.
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                Author and article information

                Contributors
                xbxurol@163.com
                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                28 June 2020
                August 2020
                : 24
                : 16 ( doiID: 10.1111/jcmm.v24.16 )
                : 9231-9243
                Affiliations
                [ 1 ] Department of Urology The Second Affiliated Hospital of Soochow University Suzhou China
                [ 2 ] Anhui Medical University Hefei China
                [ 3 ] Department of Andrology Urology Shengli Oilfield Central Hospital Dongying China
                Author notes
                [*] [* ] Correspondence

                Boxin Xue, Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

                Email: xbxurol@ 123456163.com

                Author information
                https://orcid.org/0000-0001-5037-4076
                Article
                JCMM15564
                10.1111/jcmm.15564
                7417716
                32596993
                9dd03d12-ef9b-4cce-91a4-a6c4eb49ea29
                © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 April 2020
                : 29 May 2020
                : 08 June 2020
                Page count
                Figures: 7, Tables: 1, Pages: 13, Words: 6363
                Funding
                Funded by: Youth Excellence Projects of CNNC
                Award ID: 2018‐272‐4
                Funded by: Suzhou Science and Technology Development Plan Project
                Award ID: SYS201720
                Funded by: Clinical and Medical Expert Team” Introduction Project in Suzhou
                Award ID: SZYJTD201705
                Funded by: Youth Workers Pre‐Research Fund Project of the Second Affiliated Hospital of Soochow University
                Award ID: SDFEYGJ1707
                Award ID: SDFEYQN1713
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                August 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.6 mode:remove_FC converted:11.08.2020

                Molecular medicine
                bladder cancer,gins2,lncrna,mir‐515‐5p,snhg3
                Molecular medicine
                bladder cancer, gins2, lncrna, mir‐515‐5p, snhg3

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