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      Recent advances in unraveling the molecular mechanisms and functions of HOXA11-AS in human cancers and other diseases

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          Abstract

          A large number of previously published research articles have demonstrated that the expression levels of long noncoding RNAs (lncRNAs) are generally dysregulated, either through overexpression or underexpression, in cancer and other types of disease. As a recently discovered lncRNA, HOXA11 antisense RNA (HOXA11-AS) is able to serve as an oncogenic or tumor-suppressor gene and serves a vital role in the processes of proliferation, invasion, and migration of cancer cells. HOXA11-AS appears to be a major factor contributing to epigenetic modification, and exerts transcriptional, post-transcriptional, translational and post-translational regulatory effects on genes through a variety of mechanisms; for example, by competing endogenous RNA (ceRNA) and a molecular scaffold mechanism. A number of reports have demonstrated that HOXA11-AS functions as a protein scaffold for polycomb repressive complex 2 (PRC2), lysine-specific histone demethylase 1 (LSD1) and DNA methyltransferase 1 (DNMT1) to perform epigenetic modifications on chromosomes in the nucleus. Furthermore, HOXA11-AS is also located in the cytoplasm and can act as a ceRNA, which sponges miRNAs. In addition, HOXA11-AS may be useful as a biomarker for the diagnosis and prognosis of cancer. In the present review article, the clinical value, phenotype and mechanism of HOXA11-AS in a variety of tumors types are briefly summarized, as well as its clinical value in certain additional diseases. The perspective of the authors is that HOXA11-AS may represent an effective tumor marker and therapeutic target for cancer diagnosis and therapy.

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          Gene regulation in the immune system by long noncoding RNAs

          Long non-coding RNAs (lncRNAs) are being increasingly appreciated as important regulators of gene expression. Chang and colleagues review the roles identified for lncRNAs in the immune system and discuss models for how lncRNAs mediate their effects.
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            Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

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              LncRNA HOXA11-AS Promotes Proliferation and Invasion of Gastric Cancer by Scaffolding the Chromatin Modification Factors PRC2, LSD1, and DNMT1.

              Long noncoding RNAs (lncRNA) have been implicated in human cancer but their mechanisms of action are mainly undocumented. In this study, we investigated lncRNA alterations that contribute to gastric cancer through an analysis of The Cancer Genome Atlas RNA sequencing data and other publicly available microarray data. Here we report the gastric cancer-associated lncRNA HOXA11-AS as a key regulator of gastric cancer development and progression. Patients with high HOXA11-AS expression had a shorter survival and poorer prognosis. In vitro and in vivo assays of HOXA11-AS alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, and apoptosis. Strikingly, high-throughput sequencing analysis after HOXA11-AS silencing highlighted alterations in cell proliferation and cell-cell adhesion pathways. Mechanistically, EZH2 along with the histone demethylase LSD1 or DNMT1 were recruited by HOXA11-AS, which functioned as a scaffold. HOXA11-AS also functioned as a molecular sponge for miR-1297, antagonizing its ability to repress EZH2 protein translation. In addition, we found that E2F1 was involved in HOXA11-AS activation in gastric cancer cells. Taken together, our findings support a model in which the EZH2/HOXA11-AS/LSD1 complex and HOXA11-AS/miR-1297/EZH2 cross-talk serve as critical effectors in gastric cancer tumorigenesis and progression, suggesting new therapeutic directions in gastric cancer. Cancer Res; 76(21); 6299-310. ©2016 AACR.
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                Author and article information

                Journal
                Oncol Rep
                Oncol. Rep
                Oncology Reports
                D.A. Spandidos
                1021-335X
                1791-2431
                June 2020
                19 March 2020
                19 March 2020
                : 43
                : 6
                : 1737-1754
                Affiliations
                [1 ]Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Heping, Tianjin 300052, P.R. China
                [2 ]Tianjin Customs District China, Heping, Tianjin 300041, P.R. China
                [3 ]Department of Neurosurgery, The First Affliated Hospital of Zhengzhou University, Zhengzhou, Henan 453002, P.R. China
                Author notes
                Correspondence to: Dr Lei Han, Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, 154 Anshan Road, Heping, Tianjin 300052, P.R. China, E-mail: superhanlei@ 123456hotmail.com
                Dr Yingwei Zhen, Department of Neurosurgery, The First Affliated Hospital of Zhengzhou University, 1 Jianshe Road East, Zhengzhou, Henan 453002, P.R. China, E-mail: fcczhenyw@ 123456zzu.edu.cn
                [*]

                Contributed equally

                Article
                or-43-06-1737
                10.3892/or.2020.7552
                7160552
                32236611
                4bd682bd-7411-4fd2-b185-2e555fe2dd86
                Copyright: © Wei et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 15 June 2019
                : 24 January 2020
                Categories
                Review

                long noncoding rna,hoxa11 antisense rna,competing endogenous rna,molecular scaffold

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