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      Correlation of long non-coding RNA H19 expression with cisplatin-resistance and clinical outcome in lung adenocarcinoma

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          Abstract

          The acquired drug resistance would influence the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer. The present study aimed to investigate the correlation of long non-coding RNA (lncRNA) H19 with cisplatin-resistance and clinical outcome in lung adenocarcinoma. In our study, the expression of H19 in cisplatin-resistant A549/DDP cells was unregulated. Knockdown of H19 restored the response of A549/DDP cells to cisplatin. H19-mediated chemosensitivity enhancement was associated with metastasis, induction of G0/G1 cell-cycle arrest, cell proliferation, and increased apoptosis. Furthermore, lncRNA H19 expression was significantly related to TNM stage and metastasis ( P = 0.012). Overexpression of H19 was negatively correlated with cisplatin-based chemotherapy response in patients. Patients with high H19 expression exhibited a significantly shorter median progression-free survival (PFS) [4.7 months] than the low-expression patients (6.3months) [ P = 0.002]. In summary, H19-mediated regulation of cisplatin resistance in human lung adenocarcinoma cells is demonstrated for the first time. H19 could potentially serve as a molecular marker to predict the clinical outcomes of lung adenocarcinoma patients.

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          Most cited references30

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          Non-coding RNA genes and the modern RNA world.

          S. Eddy (2001)
          Non-coding RNA (ncRNA) genes produce functional RNA molecules rather than encoding proteins. However, almost all means of gene identification assume that genes encode proteins, so even in the era of complete genome sequences, ncRNA genes have been effectively invisible. Recently, several different systematic screens have identified a surprisingly large number of new ncRNA genes. Non-coding RNAs seem to be particularly abundant in roles that require highly specific nucleic acid recognition without complex catalysis, such as in directing post-transcriptional regulation of gene expression or in guiding RNA modifications.
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            Targeting long non-coding RNAs in cancers: progress and prospects.

            Pervasive transcription occurs in the human genome to generate thousands of RNA transcripts, and accumulating evidence suggested that the RNA molecules, without protein coding ability, have important roles in diverse biological functions. Long non-coding RNA (lncRNA), with size larger than 200 nt, is a new class of the non-coding RNA that contributes to cancer development and progression. Roles for several lncRNAs in cancers have been characterized and strategies targeting them have inhibitory effects to malignant cells in vitro and in vivo. These findings point to the potential of lncRNAs as prospective novel therapeutic targets in cancers. Recent advance in biological drugs, led by nucleic acid drugs (i.e. siRNAs, antisense oligonucleotides), suggest directions for the development of cancer therapies targeting lncRNAs. Here, we discuss the characteristics of lncRNAs regarding their synthesis, stability and functional role in cells, and emphasize their unique properties that determine their molecular functions. We then discuss the association of lncRNAs with cancers, and illustrate the anticancer effects induced upon modulating the level and function of lncRNAs. We also revisit established methods for targeting RNA molecules and discuss new agents and strategies to attenuate lncRNAs in cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells.

              Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA H19 is up-regulated in hypoxic stress and in some tumors. However, the contributions of H19 to gastric cancer remain largely unknown. In this study, we assayed the H19 expression level in gastric cancer tissues by real-time PCR, and defined the biological functions by flow cytometry and RNA immunoprecipitation. We demonstrated that H19 levels were markedly increased in gastric cancer cells and gastric cancer tissues compared with normal controls. Moreover, ectopic expression of H19 increased cell proliferation, whereas H19 siRNA treatment contributed to cell apoptosis in AGS cell line. We further verified that H19 was associated with p53, and that this association resulted in partial p53 inactivation. These data suggest an important role for H19 in the molecular etiology of gastric cancer and potential application of H19 in gastric cancer therapy. © 2012 The Authors Journal compilation © 2012 FEBS.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                10 January 2017
                29 November 2016
                : 8
                : 2
                : 2558-2567
                Affiliations
                1 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, P.R. China
                2 Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, 201620, P. R. China
                3 Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, P.R. China
                4 International Medical School, Tianjin Medical University, Tianjin, 300070, P.R. China
                Author notes
                Correspondence to: Caicun Zhou, caicunzhoudr@ 123456163.com
                Article
                13708
                10.18632/oncotarget.13708
                5356823
                27911863
                61fb1727-956e-4a89-9905-e0b8c9529afb
                Copyright: © 2017 Wang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 June 2016
                : 21 November 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                long non-coding rna,lung adenocarcinoma,h19,cisplatin,a549/ddp cells
                Oncology & Radiotherapy
                long non-coding rna, lung adenocarcinoma, h19, cisplatin, a549/ddp cells

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