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      Downregulation of miR-154 in human glioma and its clinicopathological and prognostic significance

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          Abstract

          Objective

          MicroRNA-154 (miR-154) was previously reported to be downregulated in several types of human cancers and may act as a tumour suppressor. This study aimed to measure miR-154 levels and determine its clinical significance in human glioma.

          Methods

          This retrospective study analysed fresh human glioma specimens and non-neoplastic brain tissues using real-time quantitative reverse transcription–polymerase chain reaction to determine the relative levels of miR-154. The association between miR-154 levels and various clinicopathological characteristics and survival was analysed.

          Results

          A total of 115 patients with gliomas and 115 non-neoplastic brain tissues were examined. MiR-154 levels were significantly downregulated in gliomas compared with non-neoplastic brain tissues. Low levels of miR-154 were associated with high World Health Organization grade, large tumour size (≥ 5 cm), a low Karnofsky performance status score (< 80), and a shorter overall survival. Multivariate analyses using the Cox proportional hazards regression model confirmed that decreased miR-154 level was an independent predictor of a poor prognosis.

          Conclusions

          These results suggest that miR-154 downregulation may be involved in glioma formation and progression, and that miR-154 might serve as a potential prognostic biomarker for patients with this disease.

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          Most cited references15

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          MicroRNA-27b, microRNA-101 and microRNA-128 inhibit angiogenesis by down-regulating vascular endothelial growth factor C expression in gastric cancers

          Vascular Endothelial Growth Factor C (VEGF-C) has critical roles in angiogenesis in human cancers; however, the underlying mechanisms regulating VEGF-C expression remain largely unknown. In the present study, VEGF-C protein expression and the density of blood vessels or lymphatic vessels were determined by immunohistochemistry in 103 cases of gastric cancer tissues. Suppression of VEGF-C by miR-27b, miR-101 and miR-128 was investigated by luciferase assays, Western blot and ELISA. The miRNAs expression levels were detected in human gastric cancers by real-time quantitative PCR. Cell proliferation, migration and invasion assays were performed to assess the effect of miRNAs on gastric cancer cells and human umbilical vascular endothelial cells (HUVECs). Our data showed that high VEGF-C expression was significantly associated with increased tumor size, advanced TNM classification and clinical stage, higher microvessel density (MVD) and lymphatic density (LVD), as well as poor survival in patients with gastric cancer. Furthermore, VEGF-C was found to be a direct target gene of miR-27b, miR-101, and miR-128. The expression levels of the three miRNAs were inversely correlated with MVD. Overexpression of miR-27b, miR-101, or miR-128 suppressed migration, proliferation activity, and tube formation in HUVECs by repressing VEGF-C secretion in gastric cancer cells. We conclude that miR-27b, miR-101 and miR-128 inhibit angiogenesis by down-regulating VEGF-C expression in gastric cancers.
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            Correlation of microrna-372 upregulation with poor prognosis in human glioma

            MicroRNA-372 (miR-372) acts as either an oncogenic miRNA or an anti-oncomiR in various human malignancies. However, its roles in gliomas have not been elucidated. To address this problem, we here detected miR-372 expression in human gliomas and non-neoplastic brain tissues by real-time quantitative RT-PCR assay. The association of miR-372 expression with clinicopathological factors or prognosis of glioma patients was also statistically analyzed. As the results, miR-372 expression levels were significantly upregulated in glioma tissues compared to the corresponding non-neoplastic brain tissues (P<0.001). In addition, the high miR-372 expression was significantly associated with the advanced pathological grade (P=0.008) and the low Karnofsky performance score (KPS) of glioma patients (P=0.01). Moreover, the overall survival of patients with high miR-372 expression was dramatically shorter than those with low miR-372 expression (P<0.001). Furthermore, multivariate Cox regression analysis indicated that miR-372 expression was an independent prognostic factor for glioma patients (P=0.008). More importantly, subgroup analyses according to tumor pathological grade revealed that the cumulative overall survival of glioma patients with advanced pathological grades was significantly worse for high miR-372 expression group than for low miR-372 expression group (P<0.001), but no significant difference was found for patients with low pathological grades (P=0.08). Taken together, these data offer the convincing evidence for the first time that miR-372 may act as an oncogenic miRNA in gliomas and represent a potential regulator of aggressive development and a candidate prognostic marker for this malignancy, especially for advanced tumors with high pathological grades. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1707761328850011
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              Diagnosis, treatment, and prognosis of glioma: five new things.

              L. Taylor (2010)
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                Author and article information

                Journal
                J Int Med Res
                J. Int. Med. Res
                IMR
                spimr
                The Journal of International Medical Research
                SAGE Publications (Sage UK: London, England )
                0300-0605
                1473-2300
                14 July 2016
                October 2016
                : 44
                : 5
                : 994-1001
                Affiliations
                [1 ]Department of Neurology, First Hospital of Jilin University, Changchun, Jilin Province, China
                [2 ]Department of Neurology, Affiliated Hospital of Beihua University, Jilin City, Jilin Province, China
                [3 ]Department of Thoracic Surgery, Jilin Central Hospital, Jilin City, Jilin Province, China
                Author notes
                [*]Jiang Wu, Department of Neurology, First Hospital of Jilin University, 71 Xinmin Street, Changchun 132001, Jilin Province, China. Email: docwujiang@ 123456163.com
                Article
                10.1177_0300060516649487
                10.1177/0300060516649487
                5536553
                27417886
                5d63b502-6a78-4227-9a94-f14fbba61d70
                © The Author(s) 2016

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License ( http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 29 December 2015
                : 21 April 2016
                Categories
                Research Reports

                microrna-154,glioma,real-time quantitative reverse transcription–polymerase chain reaction,prognosis

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