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      Long noncoding RNA NEAT1 promotes laryngeal squamous cell cancer through regulating miR-107/CDK6 pathway.

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          Abstract

          Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays key role in the progression of some human cancers. However, the role of NEAT1 in human laryngeal squamous cell cancer (LSCC) is still unknown. We therefore investigated the expression and function of NEAT1 in LSCC.

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          Most cited references15

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          Long non-coding RNA: a new player in cancer

          Emerging evidence showed that long non-coding RNAs (lncRNAs) play important roles in a wide range of biological processes and dysregulated lncRNAs are involved in many complex human diseases, including cancer. Although a few lncRNAs’ functions in cancer have been characterized, the detailed regulatory mechanisms of majority of lncRNAs in cancer initiation and progression remain largely unknown. In this review, we summarized recent progress on the mechanisms and functions of lncRNAs in cancer, especially focusing on the oncogenic and tumor suppressive roles of the newly identified lncRNAs, and the pathways these novel molecules might be involved in. Their potentials as biomarkers for diagnosis and prognosis in cancer are also discussed in this paper.
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            Up-regulation of long noncoding RNA MALAT1 contributes to proliferation and metastasis in esophageal squamous cell carcinoma

            Background Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has been demonstrated to be an important player in various human malignancies; it is thought to promote tumor growth by cell cycle regulating. However, the roles of MALAT1 in esophageal squamous cell carcinoma(ESCC), and the mechanisms involved in cell cycle regulation remain poorly understood. Moreover, the factors contributing to its up-regulation in tumor tissues are still largely unclear. Methods Expression of MALAT1 was determined from cell lines and clinical samples by qRT-PCR. The effects of MALAT1 knockdown on cell proliferation, cell cycle, apoptosis, migration, and invasion were evaluated by in vitro and in vivo assays. The potential protein expression changes were investigated by Western-blotting. The methylation status of the CpG island in the MALAT1 promoter was explored by bisulfite sequencing, while the copy numbers in tumor tissues and blood samples were detected by a well-established AccuCopyTM method. Results MALAT1 was over-expressed in 46.3% of ESCC tissues, mostly in the high-stage tumor samples. Enhanced MALAT1 expression levels were positively correlated with clinical stages, primary tumor size, and lymph node metastasis. Inhibition of MALAT1 suppressed tumor proliferation in vitro and in vivo, as well as the migratory and invasive capacity. MALAT1 depletion also induced G2/M phase arrest and increased the percentage of apoptotic cells. Western-blotting results implicated that the ATM-CHK2 pathway which is associated with G2/M arrest was phosphorylated by MALAT1 knockdown. No effects of CpG island methylation status on MALAT1 expression were found, whereas amplification of MALAT1 was found in 22.2% of tumor tissues, which correlated significantly with its over-expression. However, neither association between tissue copy number amplification and germline copy number variation, nor correlation between germline copy number variation and ESCC risk were identified in the case–control study. Conclusions Our data suggest that MALAT1 serves as an oncogene in ESCC, and it regulates ESCC growth by modifying the ATM-CHK2 pathway. Moreover, amplification of MALAT1 in tumor tissues may play an important role for its up-regulation, and it seems that the gene amplification in tumor tissues emerges during ESCC progression, but is not derived from germline origins. Electronic supplementary material The online version of this article (doi:10.1186/s13046-015-0123-z) contains supplementary material, which is available to authorized users.
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              Combined detection of serum exosomal miR-21 and HOTAIR as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma.

              Serum exosomes containing noncoding RNA (ncRNA) play an important role in both physiological and pathological conditions. However, biological function of exosomal ncRNA remains unclear. The aim of the study was to investigate the prognostic and diagnostic values of exosomal ncRNA by comparing the amounts of exosomal miR-21 and HOTAIR in serum of laryngeal squamous cell carcinoma (LSCC) patients with those of polyps of vocal cords, and by determinating whether combined detection of the two molecules could provide useful information in the diagnosis of LSCC. Exosomes were isolated from the serum samples of 52 LSCC patients and those of 49 patients with polyps of vocal cords. TEM and Western blot were applied for the confirmation of isolated exosomes by observing the ultra structure and testing CD63 marker protein, respectively. RT-PCR was performed to detect the expression of miR-21 and HOTAIR in the exosomes. The receiver-operating characteristic (ROC) curve was generated to examine the prognostic value of the two molecules. The expression of exosomal miR-21 and HOTAIR was significantly higher in patients with LSCC than those with vocal cord polyps. There were significant differences of serum exosomal miR-21 and HOTAIR expressions between the advanced T classifications (T3/T4) or clinical stages (III/IV) and the early stages. The patients with lymph node metastasis had higher serum exosomal miR-21 and HOTAIR expressions than those without. There were no differences between patient sex, tumor locations and differentiations. The area under the ROC curve of combined examination of exosomal HOTAIR and miR-21 for diagnosing LSCC was 87.6 %, which was significantly higher than 80.1 % of miR-21 (p = 0.0359) or 72.7 % of HOTAIR (p = 0.0012), showing 94.2 and 73.5 % of sensitivity and specificity, respectively, in differentiating the malignant from benign laryngeal disease. Serum exosomal miR-21 and HOTAIR were significantly correlated with clinical parameters of LSCC, and combined evaluation of their serum expressions may be a valuable biomarker to screen LSCC and might be a promising predicting tool for LSCC patient.
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                Author and article information

                Journal
                J Exp Clin Cancer Res
                Journal of experimental & clinical cancer research : CR
                Springer Science and Business Media LLC
                1756-9966
                0392-9078
                Jan 29 2016
                : 35
                Affiliations
                [1 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. 350239591@qq.com.
                [2 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. tianshiyi.hot@163.com.
                [3 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. zhou15153887577@163.com.
                [4 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. 826108898@qq.com.
                [5 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. drhgq@hotmail.com.
                [6 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. haoyang1028@yeah.net.
                [7 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. xuanlijia1992@126.com.
                [8 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. 546181026@qq.com.
                [9 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. 76202920@qq.com.
                [10 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. hydeyebh@sina.com.
                [11 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246, Baojian Road, Harbin, 150086, China. liuming002@outlook.com.
                [12 ] Department of Otorhinolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital, Harbin Medical University, No. 213, Jianshe Road, Daqing, China. qlm8977976@163.com.
                Article
                10.1186/s13046-016-0297-z
                10.1186/s13046-016-0297-z
                4731996
                26822763
                2f189c2c-b114-4090-83cf-e15327e5a8c8
                History

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