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      Exploration of the diagnostic value and molecular mechanism of miR-1 in prostate cancer: A study based on meta-analyses and bioinformatics

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          Abstract

          Prostate cancer (PCa) remains a principal issue to be addressed in male cancer-associated mortality. Therefore, the present study aimed to examine the clinical value and associated molecular mechanism of microRNA (miR)-1 in PCa. A meta-analysis was conducted to evaluate the diagnosis of miR-1 in PCa via Gene Expression Omnibus and ArrayExpress datasets, The Cancer Genome Atlas miR-1 expression data and published literature. It was identified that expression of miR-1 was significantly downregulated in PCa. Decreased miR-1 expression possessed moderate diagnostic value, with area under the curve, sensitivity, specificity and odds ratio values at 0.73, 0.77, 0.57 and 4.60, respectively. Using bioinformatics methods, it was revealed that a number of pathways, including the ‘androgen receptor signaling pathway’, ‘androgen receptor activity’, ‘transcription factor binding’ and ‘protein processing in the endoplasmic reticulum’, were important in PCa. A total of seven hub genes, including phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccin ocarboxamide synthase (PAICS), cadherin 1 (CDH1), SRC proto-oncogene, non-receptor tyrosine kinase, twist family bHLH transcription factor 1 (TWIST1), ZW10 interacting kinetochore protein (ZWINT), PCNA clamp associated factor (KIAA0101) and androgen receptor, among which, five (PAICS, CDH1, TWIST1, ZWINT and KIAA0101) were significantly upregulated and negatively correlated with miR-1, were identified as key miR-1 target genes in PCa. Additionally, it was investigated whether miR-1 and its hub genes were associated with clinical features, including age, tumor status, residual tumor, lymph node metastasis, pathological T stage and prostate specific antigen level. Collectively the results suggest that miR-1 may be involved in the progression of PCa, and consequently be a promising diagnostic marker. The ‘androgen receptor signaling pathway’, ‘androgen receptor activity’, ‘transcription factor binding’ and ‘protein processing in the endoplasmic reticulum’ may be crucial interactive pathways in PCa. Furthermore, PAICS, CDH1, TWIST1, ZWINT and KIAA0101 may serve as crucial miR-1 target genes in PCa.

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          Exploring miRNA based approaches in cancer diagnostics and therapeutics.

          MicroRNAs (miRNAs), a highly conserved class of tissue specific, small non-protein coding RNAs maintain cell homeostasis by negative gene regulation. Proper controlling of miRNA expression is required for a balanced physiological environment, as these small molecules influence almost every genetic pathway from cell cycle checkpoint, cell proliferation to apoptosis, with a wide range of target genes. Deregulation in miRNAs expression correlates with various cancers by acting as tumor suppressors and oncogenes. Although promising therapies exist to control tumor development and progression, there is a lack of efficient diagnostic and therapeutic approaches for delineating various types of cancer. The molecularly different tumors can be differentiated by specific miRNA profiling as their phenotypic signatures, which can hence be exploited to surmount the diagnostic and therapeutic challenges. Present review discusses the involvement of miRNAs in oncogenesis with the analysis of patented research available on miRNAs.
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            Web-TCGA: an online platform for integrated analysis of molecular cancer data sets

            Background The Cancer Genome Atlas (TCGA) is a pool of molecular data sets publicly accessible and freely available to cancer researchers anywhere around the world. However, wide spread use is limited since an advanced knowledge of statistics and statistical software is required. Results In order to improve accessibility we created Web-TCGA, a web based, freely accessible online tool, which can also be run in a private instance, for integrated analysis of molecular cancer data sets provided by TCGA. In contrast to already available tools, Web-TCGA utilizes different methods for analysis and visualization of TCGA data, allowing users to generate global molecular profiles across different cancer entities simultaneously. In addition to global molecular profiles, Web-TCGA offers highly detailed gene and tumor entity centric analysis by providing interactive tables and views. Conclusions As a supplement to other already available tools, such as cBioPortal (Sci Signal 6:pl1, 2013, Cancer Discov 2:401–4, 2012), Web-TCGA is offering an analysis service, which does not require any installation or configuration, for molecular data sets available at the TCGA. Individual processing requests (queries) are generated by the user for mutation, methylation, expression and copy number variation (CNV) analyses. The user can focus analyses on results from single genes and cancer entities or perform a global analysis (multiple cancer entities and genes simultaneously). Electronic supplementary material The online version of this article (doi:10.1186/s12859-016-0917-9) contains supplementary material, which is available to authorized users.
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              Deregulation of Rab and Rab Effector Genes in Bladder Cancer

              Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                December 2018
                25 October 2018
                25 October 2018
                : 18
                : 6
                : 5630-5646
                Affiliations
                [1 ]Department of Urological Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
                [2 ]Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
                [3 ]Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
                Author notes
                Correspondence to: Dr Hai-Biao Yan, Department of Urological Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China, E-mail: yanhaibiao_gxmuyfy@ 123456163.com
                Article
                mmr-18-06-5630
                10.3892/mmr.2018.9598
                6236292
                30365107
                fb24a3b7-78bd-4f1d-93c8-5e8cd5b9be77
                Copyright: © Xie 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
                : 17 December 2017
                : 24 September 2018
                Categories
                Articles

                mir-1,pca,meta-analysis,bioinformatics,target gene,signaling pathway

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