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      LncRNA HMMR-AS1 promotes proliferation and metastasis of lung adenocarcinoma by regulating MiR-138/sirt6 axis

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          Abstract

          Purpose: Long noncoding RNAs (lncRNA) play critical roles in cancer development. In this study, we aimed to explore the function and possible molecular mechanism of HMMR-AS1 involved in lung adenocarcinoma (LUAD).

          Experimental Design: Firstly, we analyzed HMMR-AS1 expression in LUAD tissues with the sequencing data from The Cancer Genome Atlas (TCGA). Next, we evaluated the effects of HMMR-AS1 on LUAD cell proliferation and apoptosis, and its regulation of miR-138 by acting as a ceRNA. The animal model was used to support the in vitro experimental findings.

          Results: HMMR-AS1 expression was significantly upregulated in LUAD tissues and was associated with larger tumor diameter, advanced TNM stage, lymph node metastasis, and shorter survival. Knockdown of HMMR-AS1 induced apoptosis and growth arrest in vitro and inhibited tumorigenesis in mouse xenografts. Mechanistically, HMMR-AS1 functioned as a ceRNA of miR-138, thereby leading to repression of its endogenous target sirt6. Moreover, knockdown of HMMR-AS1 dramatically inhibited tumor growth and metastasis of LUAD in vivo.

          Conclusions: Taken together, HMMR-AS1 is significantly over-expressed in LUAD, and HMMR-AS1–miR-138–sirt6 axis play a critical role in LUAD tumorigenesis. Our findings highlight an oncogenic role of HMMR-AS1 in LUAD.

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          Most cited references16

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          Lnc2Cancer: a manually curated database of experimentally supported lncRNAs associated with various human cancers

          Lnc2Cancer (http://www.bio-bigdata.net/lnc2cancer) is a manually curated database of cancer-associated long non-coding RNAs (lncRNAs) with experimental support that aims to provide a high-quality and integrated resource for exploring lncRNA deregulation in various human cancers. LncRNAs represent a large category of functional RNA molecules that play a significant role in human cancers. A curated collection and summary of deregulated lncRNAs in cancer is essential to thoroughly understand the mechanisms and functions of lncRNAs. Here, we developed the Lnc2Cancer database, which contains 1057 manually curated associations between 531 lncRNAs and 86 human cancers. Each association includes lncRNA and cancer name, the lncRNA expression pattern, experimental techniques, a brief functional description, the original reference and additional annotation information. Lnc2Cancer provides a user-friendly interface to conveniently browse, retrieve and download data. Lnc2Cancer also offers a submission page for researchers to submit newly validated lncRNA-cancer associations. With the rapidly increasing interest in lncRNAs, Lnc2Cancer will significantly improve our understanding of lncRNA deregulation in cancer and has the potential to be a timely and valuable resource.
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            Long intergenic non-coding RNA 00152 promotes lung adenocarcinoma proliferation via interacting with EZH2 and repressing IL24 expression

            Background Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown. Methods Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24. Results LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD. Conclusions Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12943-017-0581-3) contains supplementary material, which is available to authorized users.
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              Review: Regulation of the cancer epigenome by long non-coding RNAs.

              Long non-coding RNAs have emerged as highly versatile players in the regulation of gene expression in development and human disease, particularly cancer. Hundreds of lncRNAs become dysregulated across tumor types, and multiple lncRNAs have demonstrated functions as tumor-suppressors or oncogenes. Furthermore, studies have demonstrated that dysregulation of lncRNAs results in alterations of the epigenome in cancer cells, potentially providing a novel mechanism for the massive epigenomic alterations observed in many tumors. Here, we highlight and provide some illustrious examples of lncRNAs in various epigenetic regulatory processes, including coordination of chromatin dynamics, regulation of DNA methylation, modulation of other non-coding RNAs and mRNA stability, and control of epigenetic substrate availability through altered tumor metabolism. In light of all these known and emerging functions in epigenetic regulation of tumorigenesis and cancer progression, lncRNAs represent attractive targets for future therapeutic strategies in cancer.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                31 May 2019
                25 May 2019
                : 11
                : 10
                : 3041-3054
                Affiliations
                [1 ]Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai 200433, , China
                [2 ]Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai 200433, , China
                [* ]Equal Contribution
                Author notes
                Correspondence to: Jiying Wang; email: jiyingwangzhe@ 123456126.com
                Article
                101958
                10.18632/aging.101958
                6555459
                31128573
                8270ea50-255f-4970-8599-1d99054ede00
                Copyright © 2019 Cai et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 March 2019
                : 03 May 2019
                Categories
                Research Paper

                Cell biology
                lung adenocarcinoma (luad),hmmr-as1,mir-138,sirt6,proliferation,apoptosis,tumorigenesis
                Cell biology
                lung adenocarcinoma (luad), hmmr-as1, mir-138, sirt6, proliferation, apoptosis, tumorigenesis

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