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      MicroRNA-197 reverses the drug resistance of fluorouracil-induced SGC7901 cells by targeting mitogen-activated protein kinase 1

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          Abstract

          MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, which serve an important function in the development of multidrug resistance in cancer through the post-transcriptional regulation of gene expression and RNA silencing. In the present study, the functional effects of miR-197 were analyzed in chemo-resistant gastric cancer cells. Low expression levels of miR-197 were observed in the fluorouracil (5-FU)-resistant gastric cell line SGC7901/5-FU when compared with those in the parental gastric cell line SGC7901. Overexpression of miR-197 in SGC7901/5-FU cells was identified to partially restore 5-FU sensitivity. miRNA target prediction algorithms suggested that mitogen-activated protein kinase 1 (MAPK1) is a candidate target gene for miR-197. A luciferase reporter assay confirmed that miR-197 led to silencing of the MAPK1 gene by recognizing and then specifically binding to the predicted site of the MAPK1 mRNA 3′-untranslated region. When miR-197 was overexpressed in SGC7901 cells, the protein levels of MAPK1 were downregulated. Furthermore, MAPK1 knockdown significantly increased the growth inhibition rate of the SGC7901/5-FU cells compared with those in the control group. These results indicated that miR-197 may influence the sensitivity of 5-FU treatment in a gastric cancer cell line by targeting MAPK1.

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          Most cited references23

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          Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study

          The Lancet, 349(9064), 1498-1504
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            Nuclear export of microRNA precursors.

            MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.
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              Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines.

              Micro-RNA (miRNA) are endogenous regulatory RNA molecules that modulate gene expression. Alterations in miRNA expression can contribute to tumor growth by modulating the functional expression of critical genes involved in tumor cell proliferation or survival. Our aims were to identify specific miRNA involved in the regulation of cholangiocarcinoma growth and response to chemotherapy. miRNA expression in malignant and nonmalignant human cholangiocytes was assessed using a microarray. Expression of selected miRNA and their precursors was evaluated by Northern blots and real-time polymerase chain reaction, respectively. The effect of selected miRNA on cell growth and response to chemotherapy was assessed using miRNA-specific antisense oligonucleotides to decrease miRNA expression or with precursor miRNA to increase cellular expression. miRNA expression was markedly different in malignant cholangiocytes, with decreased expression of many miRNA compared with nonmalignant cells. A cluster of miRNA, including miR-320, miR-200b, miR-21, miR-23a, miR-141, miR-27a, and miR-34a, were expressed in all cell lines. MiR-21, miR-141, and miR-200b were highly over-expressed in malignant cholangiocytes. Inhibition of miR-21 and miR-200b increased sensitivity to gemcitabine, whereas inhibition of miR-141 decreased cell growth. Treatment of tumor cell xenografts with systemic gemcitabine altered the expression of a significant number of miRNA. miR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-dependent activation of PI 3-kinase signaling. Potential target genes that were modulated by selected miRNA were identified. Alterations in miRNA expression contribute to tumor growth and response to chemotherapy. Aberrantly expressed miRNA or their targets will provide mechanistic insight and therapeutic targets for cholangiocarcinoma.
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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
                October 2015
                07 July 2015
                07 July 2015
                : 12
                : 4
                : 5019-5025
                Affiliations
                Department of Medical Oncology, Huizhou Municipal Central Hospital of Guangdong Province, Huizhou, Guangdong 516000, P.R. China
                Author notes
                Correspondence to: Dr Xia Yuan, Department of Medical Oncology, Huizhou Municipal Central Hospital of Guangdong Province, 41 North Eling Road, Huizhou, Guangdong 516000, P.R. China, E-mail: yuanxia20140101@ 123456163.com
                Article
                mmr-12-04-5019
                10.3892/mmr.2015.4052
                4581796
                26151540
                57ebc7b5-9a88-4beb-8a1d-9787c33fc145
                Copyright: © Xiong.

                This is an open access article distributed under the terms of a Creative Commons Attribution License

                History
                : 05 March 2014
                : 10 April 2015
                Categories
                Articles

                gastric cancer,microrna-197,5-fluorouracil resistance,mitogen-activated protein kinase 1

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