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      Long non‐coding RNA SUMO1P3 promotes hepatocellular carcinoma progression through activating Wnt/β‐catenin signalling pathway by targeting miR‐320a

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          Abstract

          In this study, we aimed to investigate expression profile of long non‐coding RNA (lncRNA) SUMO1P3, and its role and molecular mechanisms in the progression of hepatocellular carcinoma (HCC).

          The expression of SUMO1P3 in HCC tissues and cells was detected using quantitative real‐time polymerase chain reaction (qRT‐PCR). The chi‐squared test was used to estimate the relationship between SUMO1P3 levels and clinical characteristics of HCC cases. Cellular biological behaviours were investigated using MTT, transwell assays and wound healing assay. Bioinformatics and dual‐luciferase reporter assays were performed to identify potential target of SUMO1P3 in HCC. Additionally, protein analysis was carried out using Western blot.

          The expression of SUMO1P3 was significantly higher in HCC tissues and cells than in non‐cancerous specimens and normal cells ( P < .01). Moreover, its up‐regulation was closely correlated with lymph node metastasis ( P = .027) and TNM stage ( P = .019). SUMO1P3 knockdown inhibited the proliferation, migration and invasion of HCC cells. MiR‐320a was a potential target of SUMO1P3, and its expression was negatively regulated by SUMO1P3 in HCC SUMO1P3 could activate Wnt/β‐catenin pathway, which was mediated by miR‐320a.

          Elevated expression of SUMO1P3 predicts malignant progression among HCC patients. SUMO1P3 enhances Wnt/β‐catenin pathway through sponging miR‐320a, thus contributing to aggressive progression of HCC.

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          Most cited references18

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          Up-regulation of SUMO1 pseudogene 3 (SUMO1P3) in gastric cancer and its clinical association.

          Long noncoding RNAs (lncRNAs) play crucial roles during cancer occurrence and progression. The pseudogene-expressed lncRNA is one major type of lncRNA family. However, their association with cancers is largely unknown. In this study, we focused on small ubiquitin-like modifier (SUMO) 1 pseudogene 3, SUMO1P3. Gastric cancer tissues and adjacent nontumor tissues were collected from 96 patients with gastric cancer. The SUMO1P3 levels were detected by quantitative reverse transcription-polymerase chain reaction. Then, the association between the level of SUMO1P3 in gastric cancer tissues and the clinicopathological features of patients with gastric cancer was further analyzed. A receiver operating characteristic curve was constructed for differentiating patients with gastric cancer from patients with benign gastric diseases. The results showed that SUMO1P3 was significantly up-regulated in gastric cancer tissues compared with paired-adjacent nontumorous tissues (p < 0.01). Its expression level was significantly correlated with tumor size (p = 0.003), differentiation (p = 0.002), lymphatic metastasis (p = 0.001), and invasion (p = 0.039). The area under the ROC curve of SUMO1P3 was up to 0.666. These results indicated, for the first time, that pseudogene-expressed lncRNA SUMO1P3 may be a potential biomarker in the diagnosis of gastric cancer.
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            Emerging therapies in advanced hepatocellular carcinoma

            Background Prognosis is very poor for advanced HCC patients partially due to lack of effective systemic treatment. Sorafenib was the only approved agent for advanced HCC since 2007 until recent breakthroughs. In this article, we will review the newer approved and promising agents in the treatment of advanced HCC in the first line setting and beyond progression. Main body The Food and Drug Administration approved sorafenib as it demonstrated 3 months overall survival benefit compared to placebo in the first line setting over 10 years ago. Multiple single agent and combination therapies have been studied but failed to show benefit. Chemotherapy has limited role in patients with advanced HCC given poor hepatic reserve due to underlying cirrhosis. A new era of treatment for advanced HCC arrived recently with exciting data presented for lenvatinib, regorafenib, cabozantinib, nivolumab, ramucirumab and several other promising clinical trials. Conclusion Advanced HCC patients are difficult to treat with poor outcomes. After initial approval of sorafenib in 2007, we recently have multiple new agents that showed benefit and promising activity, and are set to change the landscape of HCC treatment.
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              Long noncoding RNAs: regulation, function and cancer.

              Long noncoding RNAs (lncRNAs) are non-protein-coding RNA transcripts that exert a key role in many cellular processes and have potential toward addressing disease etiology. Here, we review existing noncoding RNA classes and then describe a variety of mechanisms and functions by which lncRNAs regulate gene expression such as chromatin remodeling, genomic imprinting, gene transcription and post-transcriptional processing. We also examine several lncRNAs that contribute significantly to pathogenesis, oncogenesis, tumor suppression and cell cycle arrest of diverse cancer types and also give a summary of the pathways that lncRNAs might be involved in.
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                Author and article information

                Contributors
                ribkrdg@126.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
                22 January 2020
                March 2020
                : 24
                : 5 ( doiID: 10.1111/jcmm.v24.5 )
                : 3108-3116
                Affiliations
                [ 1 ] Department of Ultrasonography Fujian Provincial Hospital Shengli Clinical Medical College of Fujian Medical University Fuzhou China
                Author notes
                [*] [* ] Correspondence

                Songsong Wu, Department of Ultrasonography, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.

                Email: ribkrdg@ 123456126.com

                Author information
                https://orcid.org/0000-0003-0421-1465
                Article
                JCMM14977
                10.1111/jcmm.14977
                7077605
                31970876
                7dfb31a2-4463-4dda-80ba-0a3a500d092d
                © 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
                : 29 December 2018
                : 05 June 2019
                : 03 July 2019
                Page count
                Figures: 7, Tables: 1, Pages: 9, Words: 4873
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                March 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.8 mode:remove_FC converted:17.03.2020

                Molecular medicine
                hepatocellular carcinoma,long non‐coding rna,micrornas,sumo1p3,wnt/β‐catenin pathway

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