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      Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression

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          Abstract

          Recently, long noncoding RNAs have been emerged as critical regulators of human disease and prognostic markers in several cancers, including gastric cancer. In this study, we globally assessed the transcriptomic differences of lncRNAs in gastric cancer using publicly available microarray data from Gene Expression Omnibus (GEO) and identified an oncogenetic lncRNA ZFAS1, which may promote gastric tumorigenesis. ZFAS1 has been found to be upregulated and function as oncogene in colorectal cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in gastric cancer is still undetermined. Here, we reported that ZFAS1 expression is also overexpressed in gastric cancer, and its increased level is associated with poor prognosis and shorter survival. Knockdown of ZFAS1 impaired gastric cancer cells proliferation and induced apoptosis in vitro, and inhibited tumorigenicity of gastric cancer cells in vivo. Mechanistically, RNA immunoprecipitation and RNA pull-down experiment showed that ZFAS1 could simultaneously interact with EZH2 and LSD1/CoREST to repress underlying targets KLF2 and NKD2 transcription. In addition, rescue experiments determined that ZFAS1 oncogenic function is partly dependent on repressing KLF2 and NKD2. Taken together, our findings illuminate how ZFAS1 over-expression confers an oncogenic function in gastric cancer.

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          Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a

          Long noncoding RNAs are involved in diseases including cancer. Here, we reported that ANRIL (CDKN2B-AS1), a 3.8-kb long noncoding RNA, recruiting and binding to PRC2, was generally upregulated in human gastric cancer (GC) tissues. In a cohort of 120 GC patients, the higher expression of ANRIL was significantly correlated with a higher TNM stage (P=0.041) and tumor size (P=0.001). Multivariate analyses revealed that ANRIL expression served as an independent predictor for overall survival (P=0.036). Further experiments revealed that ANRIL knockdown significantly repressed the proliferation both in vitro and in vivo. We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is in part due to epigenetic repression of miR-99a/miR-449a in Trans (controlling the targets—mTOR and CDK6/E2F1 pathway) by binding to PRC2, thus forming a positive feedback loop, continuing to promote GC cell proliferation. To our knowledge, this is the first report showed that the role of ANRIL in the progression of GC and ANRIL could crosstalk with microRNAs in epigenetic level. Our results suggest that ANRIL, as a growth regulator, may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.
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            Long noncoding RNAs in development and cancer: potential biomarkers and therapeutic targets

            Long noncoding RNAs are emerging as key players in various fundamental biological processes. We highlight the varied molecular mechanisms by which lncRNAs modulate gene expression in diverse cellular contexts and their role in early mammalian development in this review. Furthermore, it is being increasingly recognized that altered expression of lncRNAs is specifically associated with tumorigenesis, tumor progression and metastasis. We discuss various lncRNAs implicated in different cancer types with a focus on their clinical applications as potential biomarkers and therapeutic targets in the pathology of diverse cancers.
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              (O.) Andersen, (D.T.T.) Haug (edd.) Relative Chronology in Early Greek Epic Poetry. Pp. xiv + 277, figs. Cambridge: Cambridge University Press, 2012. Cased, £60, US$99. ISBN: 978-0-521-19497-6.

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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                13 June 2017
                26 May 2016
                : 8
                : 24
                : 38227-38238
                Affiliations
                1 Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China
                2 Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, People's Republic of China
                3 Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, People's Republic of China
                4 Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA
                5 Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China
                6 Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
                Author notes
                Correspondence to: Ming Sun, msun7@ 123456mdanderson.org
                [*]

                These authors contributed equally to this work and should be regarded as joint first authors

                Article
                9611
                10.18632/oncotarget.9611
                5503528
                27246976
                9938df4c-96ba-499c-a2e8-f35fc354ec49
                Copyright: © 2017 Nie et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 10 February 2016
                : 2 May 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                long noncoding rna,zfas1,gastric cancer,proliferation,klf2 and nkd2
                Oncology & Radiotherapy
                long noncoding rna, zfas1, gastric cancer, proliferation, klf2 and nkd2

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