MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1

Glioma proliferation is a multistep process during which a sequence of genetic and epigenetic alterations randomly occur to affect the genes controlling cell proliferation, cell death and genetic stability. microRNAs are emerging as important epigenetic modulators of multiple target genes, leading t...

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Veröffentlicht in:PloS one 2013-01, Vol.8 (1), p.e54932
Hauptverfasser: Hui, Wang, Yuntao, Lu, Lun, Luo, WenSheng, Li, ChaoFeng, Liang, HaiYong, He, Yueyang, Ba
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Yuntao, Lu
Lun, Luo
WenSheng, Li
ChaoFeng, Liang
HaiYong, He
Yueyang, Ba
description Glioma proliferation is a multistep process during which a sequence of genetic and epigenetic alterations randomly occur to affect the genes controlling cell proliferation, cell death and genetic stability. microRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers.In the present study, we found that expression of miR-195 was markedly downregulated in glioma cell lines and human primary glioma tissues, compared to normal human astrocytes and matched non-tumor associated tissues. Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb) and proliferating cell nuclear antigen (PCNA) in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3'-untranslated regions (3'-UTR) of cyclin D1 and cyclin E1 mRNA. Taken together, our results suggest that miR-195 plays an important role to inhibit the proliferation of glioma cells, and present a novel mechanism for direct miRNA-mediated suppression of cyclin D1 and cyclin E1 in glioma.
doi_str_mv 10.1371/journal.pone.0054932
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Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb) and proliferating cell nuclear antigen (PCNA) in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3'-untranslated regions (3'-UTR) of cyclin D1 and cyclin E1 mRNA. Taken together, our results suggest that miR-195 plays an important role to inhibit the proliferation of glioma cells, and present a novel mechanism for direct miRNA-mediated suppression of cyclin D1 and cyclin E1 in glioma.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0054932</identifier><identifier>PMID: 23383003</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>3' Untranslated regions ; 3' Untranslated Regions - genetics ; Analysis ; Angiogenesis ; Animals ; Apoptosis ; Astrocytes ; Astrocytes - cytology ; Astrocytes - metabolism ; Base Sequence ; Biology ; Biomarkers, Tumor - metabolism ; Brain cancer ; Brain tumors ; Breast cancer ; Cancer ; Cell cycle ; Cell death ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cloning ; Control stability ; Cyclin D1 ; Cyclin D1 - genetics ; Cyclin E - genetics ; Cyclin-dependent kinases ; Cytometry ; Down-Regulation - genetics ; Ectopic expression ; Epigenetic inheritance ; Flow cytometry ; Gene expression ; Genes ; Glioma ; Glioma - genetics ; Glioma - pathology ; Glioma cells ; Gliomas ; Hepatology ; Humans ; Kinases ; Liver cancer ; Medical prognosis ; Medicine ; Metastasis ; Mice ; Mice, Inbred BALB C ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Modulators ; mRNA ; Neurosurgery ; Oncogene Proteins - genetics ; Phosphorylation ; Proliferating cell nuclear antigen ; Proliferating Cell Nuclear Antigen - metabolism ; Proteins ; Retina ; Retinoblastoma ; Ribonucleic acid ; RNA ; S phase ; Signaling ; Tissues ; Wang Hui</subject><ispartof>PloS one, 2013-01, Vol.8 (1), p.e54932</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Hui et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb) and proliferating cell nuclear antigen (PCNA) in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3'-untranslated regions (3'-UTR) of cyclin D1 and cyclin E1 mRNA. 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genetics</subject><subject>Phosphorylation</subject><subject>Proliferating cell nuclear antigen</subject><subject>Proliferating Cell Nuclear Antigen - metabolism</subject><subject>Proteins</subject><subject>Retina</subject><subject>Retinoblastoma</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>S phase</subject><subject>Signaling</subject><subject>Tissues</subject><subject>Wang Hui</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2LEzEUhgdR3HX1H4gGBMGL1nzMV26Esq5aWF1YP25DJpPMpGaSmmTE_ntTO106oCC5OMnJc96cHN4se4rgEpEKvd640Vtulltn5RLCIqcE38vOUQqLEkNy_2R_lj0KYZMgUpflw-wME1ITCMl59v2jFt7dflotEC2Atr1udAwg9hJsvTNaSc-jdhY4Bfpx4BZ0RruBAyGNCaDZgVZ7KaLZgch9J6O2HRA7YbQFbxHgtj2ertDj7IHiJsgnU7zIvr67-nL5YXF98359ubpeiJLiuBAK4VY0FUIS40ZAiigqValEVeUtRGWJZF60uaqKAjWYNCVtBC3qAkpeY97U5CJ7ftDdGhfYNKfAEMEVrWGdk0SsD0Tr-IZtvR643zHHNfuTcL5j3EctjGSwohA3itacirwmiKNWEEGRFDmFVOVJ68302tgMshXSRs_NTHR-Y3XPOveTkaKoMKVJ4MUk4N2PUYb4j5YnquOpK22VS2Ji0EGwVV5VtCxJtf_68i9UWq0ctEhOUTrlZwWvZgWJifJX7PgYAlt_vv1_9ubbnH15wvaSm9gHZ8a9l8IczA9gsmEIXqq7ySHI9kY_ToPtjc4mo6eyZ6dTvys6Opv8BoNJ93s</recordid><startdate>20130128</startdate><enddate>20130128</enddate><creator>Hui, Wang</creator><creator>Yuntao, Lu</creator><creator>Lun, Luo</creator><creator>WenSheng, Li</creator><creator>ChaoFeng, Liang</creator><creator>HaiYong, He</creator><creator>Yueyang, Ba</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130128</creationdate><title>MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1</title><author>Hui, Wang ; Yuntao, Lu ; Lun, Luo ; WenSheng, Li ; ChaoFeng, Liang ; HaiYong, He ; Yueyang, Ba</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-cf12dcb711e22bc091916f6fc774d01661e45d4f7551b23b69bc95850ea82ab83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3' Untranslated regions</topic><topic>3' Untranslated Regions - 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Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb) and proliferating cell nuclear antigen (PCNA) in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3'-untranslated regions (3'-UTR) of cyclin D1 and cyclin E1 mRNA. Taken together, our results suggest that miR-195 plays an important role to inhibit the proliferation of glioma cells, and present a novel mechanism for direct miRNA-mediated suppression of cyclin D1 and cyclin E1 in glioma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23383003</pmid><doi>10.1371/journal.pone.0054932</doi><tpages>e54932</tpages><oa>free_for_read</oa></addata></record>
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subjects 3' Untranslated regions
3' Untranslated Regions - genetics
Analysis
Angiogenesis
Animals
Apoptosis
Astrocytes
Astrocytes - cytology
Astrocytes - metabolism
Base Sequence
Biology
Biomarkers, Tumor - metabolism
Brain cancer
Brain tumors
Breast cancer
Cancer
Cell cycle
Cell death
Cell growth
Cell Line, Tumor
Cell Proliferation
Cell Transformation, Neoplastic
Cloning
Control stability
Cyclin D1
Cyclin D1 - genetics
Cyclin E - genetics
Cyclin-dependent kinases
Cytometry
Down-Regulation - genetics
Ectopic expression
Epigenetic inheritance
Flow cytometry
Gene expression
Genes
Glioma
Glioma - genetics
Glioma - pathology
Glioma cells
Gliomas
Hepatology
Humans
Kinases
Liver cancer
Medical prognosis
Medicine
Metastasis
Mice
Mice, Inbred BALB C
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Modulators
mRNA
Neurosurgery
Oncogene Proteins - genetics
Phosphorylation
Proliferating cell nuclear antigen
Proliferating Cell Nuclear Antigen - metabolism
Proteins
Retina
Retinoblastoma
Ribonucleic acid
RNA
S phase
Signaling
Tissues
Wang Hui
title MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1
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