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      MicroRNA-155 increases colon cancer chemoresistance to cisplatin by targeting forkhead box O3

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          Abstract

          To investigate the effect of microRNA (miR)-155 on colon cancer chemoresistance to cisplatine and its mechanism. Reverse transcription quantitative polymerase chain reaction was used to measure the levels of miR-155 and forkhead box O3 (FOXO3) in colon cancer specimens and cell lines. Overexpression of miR-155 and miR-155 inhibitor were transfected into colon cancer cell lines to investigate its role of chemoresistance to cisplatin in colon cancer. MTS assays were used to analyse cell viability in vitro. In vivo tumor formation assays were performed in C57BL/6 wild type and miR-155 knockout mice (miR-155-/-). A luciferase reporter assay was used to measure the translation of FOXO3. Additionally, the expression of FOXO3 was detected by western blot analysis. It was identified that miR-155 was markedly upregulated in colon cancer tissue and cell lines. Overexpression of miR-155 enhanced colon cancer cell chemoresistance to cisplatin in vitro and tumorigenesis in vivo. In addition, overexpression of miR-155 was associated with decreased levels of FOXO3, primarily through inhibiting the expression of FOXO3 to increase colon cancer resistanec to cisplatin. The present study demonstrated that miR-155 increased colon cancer drug resistance and decreased FOXO3 expression in vivo and in vitro. This may provide a novel method for the treatment of drug-resistant colon cancer.

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          Most cited references37

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          MicroRNA biogenesis: coordinated cropping and dicing.

          V Kim (2005)
          The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, approximately 22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks.
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            MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias.

            Little is known about the expression levels or function of micro-RNAs (miRNAs) in normal and neoplastic cells, although it is becoming clear that miRNAs play important roles in the regulation of gene expression during development [Ambros, V. (2003) Cell 113, 673-676; McManus, M. T. (2003) Semin. Cancer Biol. 13, 253-258]. We now report the genomewide expression profiling of miRNAs in human B cell chronic lymphocytic leukemia (CLL) by using a microarray containing hundreds of human precursor and mature miRNA oligonucleotide probes. This approach allowed us to identify significant differences in miRNome expression between CLL samples and normal CD5+ B cells; data were confirmed by Northern blot analyses and real-time RT-PCR. At least two distinct clusters of CLL samples can be identified that were associated with the presence or absence of Zap-70 expression, a predictor of early disease progression. Two miRNA signatures were associated with the presence or absence of mutations in the expressed Ig variableregion genes or with deletions at 13q14, respectively. These data suggest that miRNA expression patterns have relevance to the biological and clinical behavior of this leukemia.
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              Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice.

              MicroRNAs (miRNAs) represent a newly discovered class of posttranscriptional regulatory noncoding small RNAs that bind to targeted mRNAs and either block their translation or initiate their degradation. miRNA profiling of hematopoietic lineages in humans and mice showed that some miRNAs are differentially expressed during hematopoietic development, suggesting a role in hematopoietic cell differentiation. In addition, recent studies suggest the involvement of miRNAs in the initiation and progression of cancer. miR155 and BIC, its host gene, have been reported to accumulate in human B cell lymphomas, especially in diffuse large B cell lymphomas, Hodgkin lymphomas, and certain types of Burkitt lymphomas. Here, we show that E(mu)-mmu-miR155 transgenic mice exhibit initially a preleukemic pre-B cell proliferation evident in spleen and bone marrow, followed by frank B cell malignancy. These findings indicate that the role of miR155 is to induce polyclonal expansion, favoring the capture of secondary genetic changes for full transformation.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                April 2018
                07 February 2018
                07 February 2018
                : 15
                : 4
                : 4781-4788
                Affiliations
                [1 ]Department of General Surgery, The People's Hospital of Rizhao City, Rizhao, Shandong 276800, P.R. China
                [2 ]Department of Urology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China
                Author notes
                Correspondence to: Professor Yuewen Gao, Department of General Surgery, The People's Hospital of Rizhao City, 126 Taian Road, Rizhao, Shandong 276800, P.R. China, E-mail: tjjkh@ 123456qq.com
                Article
                OL-0-0-7976
                10.3892/ol.2018.7976
                5840649
                29552117
                47e8713b-8f71-4774-9b13-e1fdaa247eeb
                Copyright: © Gao 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
                : 08 November 2016
                : 23 November 2017
                Categories
                Articles

                Oncology & Radiotherapy
                colon cancer,microrna-155,forkhead box o3,chemoresistance,cisplatin
                Oncology & Radiotherapy
                colon cancer, microrna-155, forkhead box o3, chemoresistance, cisplatin

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