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      The microRNA-1246 promotes metastasis in non-small cell lung cancer by targeting cytoplasmic polyadenylation element-binding protein 4

      research-article
      , ,
      Diagnostic Pathology
      BioMed Central
      miR-1246, CPEB4, NSCLC, Metastasis

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          Abstract

          Background

          The microRNAs present a class of non-coding RNAs which are usually implicated in tumor biology. Recent report has unraveled that a novel member of microRNA family called miR-1246. However, the functional role and molecular mechanisms of miR-1246 in non-small cell lung cancer (NSCLC) is still elusive.

          Methods

          Using RT-PCR, luciferase reporter, mRNA microarrays, invasion and migration assays, we investigated the potential role of miR-1246 in the pathogenesis of NSCLC.

          Results

          In this study, we showed that miR-1246 markedly promoted NSCLC cell migration and invasion. Meanwhile, we found that cytoplasmic polyadenylation element binding protein 4 (CPEB4) might be involved and serve as a direct target of miR-1246 in NSCLC. CPEB4 knockdown substantially enhanced NSCLC migration and invasion resembling the effect of miR-1246 in NSCLC. CPEB4 is also frequently downregulated in NSCLC and decreased CPEB4 expression correlated with poor survival.

          Conclusions

          These results suggested that the miR-1246 may promote cell metastasis by targeting CPEB4. Meanwhile, the level of CPEB4 could be used as a potential marker in NSCLC patients. Our findings unraveled novel functions of miR-1246 in lung cancer cells and shed light on NSCLC prognosis.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13000-015-0366-1) contains supplementary material, which is available to authorized users.

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          Most cited references19

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          Reduced accumulation of specific microRNAs in colorectal neoplasia.

          Short non-coding RNAs are known to regulate cellular processes including development, heterochromatin formation, and genomic stability in eukaryotes. Given the impact of these processes on cellular identity, a study was undertaken to investigate possible changes in microRNA (miRNA) levels during tumorigenesis. A total of 28 different miRNA sequences was identified in a colonic adenocarcinoma and normal mucosa, including 3 novel sequences and a further 7 that had previously been cloned only from mice. Human homologues of murine miRNA sequences, miR-143 and miR-145, consistently display reduced steady-state levels of the mature miRNA at the adenomatous and cancer stages of colorectal neoplasia.
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            MicroRNAs: predictors and modifiers of chemo- and radiotherapy in different tumour types.

            MicroRNAs (miRNAs) represent a class of naturally occurring small non-coding RNA molecules. They regulate gene expression at the post-transcriptional level and control thereby cellular mechanisms including developmental transitions, organ morphology, apoptosis and cell proliferation. As might be expected from molecules with these roles, miRNAs are involved in cancer development, and deregulation of several miRNAs has been found in various cancer types. Some miRNAs modulate expression of known oncogenes or tumour suppressor genes whereas others function as so called onco-miRs or tumour-suppressor-miRs. Recently, miRNAs have been studied as potential diagnostic or therapeutic targets in cancer treatment. There is increasing interest in an association between miRNA expression in tumours and chemo- and radiosensitivity, both with regards to predicting or modulating sensitivity. And indeed, different miRNAs have been found to predict sensitivity to anticancer treatment: miR-30c, miR-130a and miR-335 are downregulated in various chemoresistant cell lines, hsa-Let-7g and hsa-miR-181b are strongly associated with response to 5-fluorouracil-based antimetabolite S-1. In addition, several miRNAs were shown to influence sensitivity to chemo- or radiotherapy: miRNAs of the Let-7 family induced radiosensitivity in vitro/in vivo, inhibition of miR-21 and miR-200b increased sensitivity to gemcitabine in cholangiocarcinoma cell lines, and restoration of miR-34 in p53-deficient human gastric cancer cells induced chemosensitisation. This article summarises the current literature describing the impact of miRNAs on prediction and modification of anticancer treatment including the possible intracellular pathways involved in these processes. Copyright 2009 Elsevier Ltd. All rights reserved.
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              High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma.

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                Author and article information

                Contributors
                manuhuangweihua@163.com
                manulihuifen@163.com
                86-20-61650242 , jackieluorongcheng@163.com
                Journal
                Diagn Pathol
                Diagn Pathol
                Diagnostic Pathology
                BioMed Central (London )
                1746-1596
                25 July 2015
                25 July 2015
                2015
                : 10
                : 127
                Affiliations
                [ ]TCM-Integrated Hospital, Southern Medical University, Cancer Center, NO.13 Shiliugang Road, Haizhu District, Guangzhou, Guangdong 510315 China
                [ ]Department of Chemotherapy, Zhongshan People’s Hospital, Zhongshan, Guangdong 528400 China
                Article
                366
                10.1186/s13000-015-0366-1
                4514963
                8e648d02-6d65-48f7-8605-a65b182d79c3
                © Huang et al. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 20 June 2015
                : 15 July 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Pathology
                mir-1246,cpeb4,nsclc,metastasis
                Pathology
                mir-1246, cpeb4, nsclc, metastasis

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