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      TGF-β1 regulating miR-205/miR-195 expression affects the TGF-β signal pathway by respectively targeting SMAD2/SMAD7

      research-article
      ,
      Oncology Reports
      D.A. Spandidos
      transforming growth factor-β, miR-205, miR-195, SMAD, glioma

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          Abstract

          Transforming growth factor-β (TGF-β) proteins are important cytokines in the occurrence and development of tumors. However, its neural functions in glioma are still not understood. In the present study, we evaluated the effects of TGF-β1 on glioma cell line U87. miR-205 and miR-195 were involved in TGF-β1 signaling pathway. Quantitative real-time PCR was used to detect miR-205 and miR-195 levels in human glioma tissue samples and U87 cells treated with different concentrations of TGF-β1. Enzyme-linked immunosorbent assay (ELISA) was performed to determine TGF-β1 in the glioma patients peripheral blood. In vitro, U87 cells were transfected with mimics or inhibitors of miR-205 and miR-195. SMAD proteins were assayed by western blotting. Luciferase assay and co-immunoprecipitation (Co-IP) were used to determine the relationships between miR-205 and SMAD2, miR-195 and SMAD7. Effects of miR-205 and miR-195 on glioma cell proliferation and invasion using colony forming and cell migration assays. It was shown that miR-205 was decreased in glioma tissue, but miR-195 and TGF-β1 was increased. In addition, TGF-β1 concentration was negatively correlated with miR-205 mRNA level, but positively correlated with miR-195 mRNA. In addition, miR-205 was downregulated and miR-195 was upregulated by TGF-β1 in a dose-dependent manner. miR-205 and miR-195 targeted and inhibited SMAD2 and SMAD7 expression, respectively, in U87. High expression of miR-205 but not miR-195 reduced SMAD2 and SMAD4 heteromer formation. In addition, it was also shown that miR-205 overexpression inhibited U87 proliferation and invasion efficiently. All the results suggested that miR-205 and miR-195 participated in the TGF-β1 signaling pathway and showed opposite effects in glioma. These findings contribute to the understanding of TGF-β1 function in glioma.

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          Most cited references33

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          Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer.

          MicroRNAs (miRNAs) are a new class of short noncoding regulatory RNAs (18-25 nucleotides) that are involved in diverse developmental and pathologic processes. Altered miRNA expression has been associated with several types of human cancer. However, most studies did not establish whether miRNA expression changes occurred within cells undergoing malignant transformation. To obtain insight into miRNA deregulation in breast cancer, we implemented an in situ hybridization (ISH) method to reveal the spatial distribution of miRNA expression in archived formalin-fixed, paraffin-embedded specimens representing normal and tumor tissue from >100 patient cases. Here, we report that expression of miR-145 and miR-205 was restricted to the myoepithelial/basal cell compartment of normal mammary ducts and lobules, whereas their accumulation was reduced or completely eliminated in matching tumor specimens. Conversely, expression of other miRNAs was detected at varying levels predominantly within luminal epithelial cells in normal tissue; expression of miR-21 was frequently increased, whereas that of let-7a was decreased in malignant cells. We also analyzed the association of miRNA expression with that of epithelial markers; prognostic indicators such as estrogen receptor, progesterone receptor, and HER2; as well as clinical outcome data. This ISH approach provides a more direct and informative assessment of how altered miRNA expression contributes to breast carcinogenesis compared with miRNA expression profiling in gross tissue biopsies. Most significantly, early manifestation of altered miR-145 expression in atypical hyperplasia and carcinoma in situ lesions suggests that this miRNA may have a potential clinical application as a novel biomarker for early detection.
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            The dynamic roles of TGF-β in cancer.

            The transforming growth factor-β (TGF-β) signalling pathway plays a critical and dual role in the progression of human cancer. During the early phase of tumour progression, TGF-β acts as a tumour suppressor, exemplified by deletions or mutations in the core components of the TGF-β signalling pathway. On the contrary, TGF-β also promotes processes that support tumour progression such as tumour cell invasion, dissemination, and immune evasion. Consequently, the functional outcome of the TGF-β response is strongly context-dependent including cell, tissue, and cancer type. In this review, we describe the molecular signalling pathways employed by TGF-β in cancer and how these, when perturbed, may lead to the development of cancer. Concomitantly with our increased appreciation of the molecular mechanisms that govern TGF-β signalling, the potential to therapeutically target specific oncogenic sub-arms of the TGF-β pathway increases. Indeed, clinical trials with systemic TGF-β signalling inhibitors for treatment of cancer patients have been initiated. However, considering the important role of TGF-β in cardiovascular and many other tissues, careful screening of patients is warranted to minimize unwanted on-target side effects. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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              Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR.

              microRNA (miRNA) expression profiles are being intensively investigated for their involvement in carcinogenesis. We evaluated the prognostic value of mature microRNA-21 (miR-21) and mature microRNA-205 (miR-205) overexpression in non-small cell lung cancer (NSCLC). We studied 48 pairs of NSCLC fresh frozen tissue specimens collected at time of surgery and before chemotherapy. Highly specific amplification and quantification of mature miR-21 and mature miR-205 was achieved using looped real time RT-PCR. miRNA expression, determined by real time RT-PCR, was defined by DeltaDeltaCt measurements. We detected overexpression of mature miR-21 in 25 (52.0%) of the 48 NSCLC paired specimens and overexpression of miR-205 in 31 (64.6%). Overexpression was assessed after comparison of miRNA expression in NSCLC tissues and in their corresponding noncancerous tissues with respect to U6 expression. During the follow-up period, 29 of 48 (60.4%) patients relapsed, and 23 of 48 died (47.9%). Mature miR-21 was upregulated in 16 of 29 (55.2%) patients who relapsed and 15 of 23 (65.2%) patients who died. Mature miR-205 was overexpressed in 19 of 29 patients who relapsed (65.5%) and 15 of 23 patients who died (65.2%). Mature miR-21 overexpression correlated with overall survival (OS) of the patients (P = 0.027), whereas overexpression of mature miR-205 did not. Our results suggest that overexpression of mature miR-21 is an independent negative prognostic factor for OS in NSCLC patients.
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                Author and article information

                Journal
                Oncol Rep
                Oncol. Rep
                Oncology Reports
                D.A. Spandidos
                1021-335X
                1791-2431
                October 2016
                17 August 2016
                17 August 2016
                : 36
                : 4
                : 1837-1844
                Affiliations
                Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China
                Author notes
                Correspondence to: Dr Qianxue Chen, Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University, 99 Wuchang, 238 Jiefang Road, Wuhan, Hubei 430060, P.R. China, E-mail: qxchenwhu@ 123456yeah.net
                Article
                or-36-04-1837
                10.3892/or.2016.5023
                5022901
                27574009
                2e2f32de-cccc-463d-901b-eb4ee5c93221
                Copyright: © Duan 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
                : 30 March 2016
                : 09 August 2016
                Categories
                Articles

                transforming growth factor-β,mir-205,mir-195,smad,glioma
                transforming growth factor-β, mir-205, mir-195, smad, glioma

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