Clinical significance of microRNA-34b expression in pediatric acute leukemia
The present study aimed to explore the function of miR-34b promoter methylation in cell proliferation in children's acute leukemia. Quantitative PCR and methylation-specific PCR were performed to measure the levels of miR-34b and its promoter methylation in normal cells, eight leukemia cell lin...
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| Veröffentlicht in: | Molecular medicine reports 2016-03, Vol.13 (3), p.2777-2784 |
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| creator | CAO, LAN WANG, NA PAN, JIAN HU, SHAOYAN ZHAO, WENLI HE, HAILONG WANG, YI GU, GUIXIONG CHAI, YIHUAN |
| description | The present study aimed to explore the function of miR-34b promoter methylation in cell proliferation in children's acute leukemia. Quantitative PCR and methylation-specific PCR were performed to measure the levels of miR-34b and its promoter methylation in normal cells, eight leukemia cell lines as well as primary leukemic cells isolated from patients newly diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed lymphocytic lymphoma. miR-34b levels in leukemia cell lines and primary leukemic cells were significantly lower than those in normal cells. The miR-34b promoter was found to be methylated in all leukemia cell lines, 24 of 31 ALL patients and 8 of 19 AML patients, but not in the 23 normal controls. miR-34b expression and methylation of its promoter were not associated with most clinical parameters assessed; however, miR-34b levels in prednisone-sensitive ALL were significantly different from those in insensitive ALL. A cell counting kit-8 assay showed that transfection of miR-34b mimics into K562 cells inhibited their proliferation. Furthermore, treatment with the demethylating agent 5-aza-2-deoxycytidine significantly enhanced miR-34b expression levels and decreased the methylation status of its promoter in HL-60 and K562 cells. In conclusion, the results of the present study indicated that in pediatric leukemia cells and leukemia cell lines, the expression of miR-34b is inhibited by methylation of its promoter, which impairs the restraining effects of miR-34b on cell proliferation. It was also indicated that the expression of miR-34b in ALL patients may affect their response to early treatments. |
| doi_str_mv | 10.3892/mmr.2016.4876 |
| format | Article |
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Quantitative PCR and methylation-specific PCR were performed to measure the levels of miR-34b and its promoter methylation in normal cells, eight leukemia cell lines as well as primary leukemic cells isolated from patients newly diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed lymphocytic lymphoma. miR-34b levels in leukemia cell lines and primary leukemic cells were significantly lower than those in normal cells. The miR-34b promoter was found to be methylated in all leukemia cell lines, 24 of 31 ALL patients and 8 of 19 AML patients, but not in the 23 normal controls. miR-34b expression and methylation of its promoter were not associated with most clinical parameters assessed; however, miR-34b levels in prednisone-sensitive ALL were significantly different from those in insensitive ALL. A cell counting kit-8 assay showed that transfection of miR-34b mimics into K562 cells inhibited their proliferation. Furthermore, treatment with the demethylating agent 5-aza-2-deoxycytidine significantly enhanced miR-34b expression levels and decreased the methylation status of its promoter in HL-60 and K562 cells. In conclusion, the results of the present study indicated that in pediatric leukemia cells and leukemia cell lines, the expression of miR-34b is inhibited by methylation of its promoter, which impairs the restraining effects of miR-34b on cell proliferation. It was also indicated that the expression of miR-34b in ALL patients may affect their response to early treatments.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2016.4876</identifier><identifier>PMID: 26861642</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Acute lymphoblastic leukemia ; Acute myeloid leukemia ; Adolescent ; Age ; Blood ; Bone marrow ; Case-Control Studies ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Chemotherapy ; Child ; Child, Preschool ; Children ; Children & youth ; Chromosomes ; Clinical significance ; CpG Islands ; Dehydrogenases ; Deoxyribonucleic acid ; Development and progression ; DNA ; DNA Methylation ; Down-Regulation ; Epigenetics ; Female ; Females ; Gene expression ; Gene Expression Regulation, Leukemic ; Genetic aspects ; Health aspects ; HL-60 Cells ; Humans ; Infant ; K562 Cells ; Leukemia ; leukemia cell proliferation ; Leukemia in children ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - metabolism ; Lymphatic leukemia ; Lymphoma ; Male ; Medical prognosis ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Myeloid leukemia ; Ovarian cancer ; Pathogenesis ; Pediatrics ; Polymerase chain reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Prednisone ; Promoter Regions, Genetic ; Properties ; RNA Interference ; Standard deviation ; Transfection ; Tumor cell lines</subject><ispartof>Molecular medicine reports, 2016-03, Vol.13 (3), p.2777-2784</ispartof><rights>Copyright © 2016, Spandidos Publications</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-cc2f077fe9381412ce4e9079ffe927c6171f5f3b61d832e1947e7f20d64b837d3</citedby><cites>FETCH-LOGICAL-c459t-cc2f077fe9381412ce4e9079ffe927c6171f5f3b61d832e1947e7f20d64b837d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,5571,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26861642$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CAO, LAN</creatorcontrib><creatorcontrib>WANG, NA</creatorcontrib><creatorcontrib>PAN, JIAN</creatorcontrib><creatorcontrib>HU, SHAOYAN</creatorcontrib><creatorcontrib>ZHAO, WENLI</creatorcontrib><creatorcontrib>HE, HAILONG</creatorcontrib><creatorcontrib>WANG, YI</creatorcontrib><creatorcontrib>GU, GUIXIONG</creatorcontrib><creatorcontrib>CHAI, YIHUAN</creatorcontrib><title>Clinical significance of microRNA-34b expression in pediatric acute leukemia</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>The present study aimed to explore the function of miR-34b promoter methylation in cell proliferation in children's acute leukemia. Quantitative PCR and methylation-specific PCR were performed to measure the levels of miR-34b and its promoter methylation in normal cells, eight leukemia cell lines as well as primary leukemic cells isolated from patients newly diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed lymphocytic lymphoma. miR-34b levels in leukemia cell lines and primary leukemic cells were significantly lower than those in normal cells. The miR-34b promoter was found to be methylated in all leukemia cell lines, 24 of 31 ALL patients and 8 of 19 AML patients, but not in the 23 normal controls. miR-34b expression and methylation of its promoter were not associated with most clinical parameters assessed; however, miR-34b levels in prednisone-sensitive ALL were significantly different from those in insensitive ALL. A cell counting kit-8 assay showed that transfection of miR-34b mimics into K562 cells inhibited their proliferation. Furthermore, treatment with the demethylating agent 5-aza-2-deoxycytidine significantly enhanced miR-34b expression levels and decreased the methylation status of its promoter in HL-60 and K562 cells. In conclusion, the results of the present study indicated that in pediatric leukemia cells and leukemia cell lines, the expression of miR-34b is inhibited by methylation of its promoter, which impairs the restraining effects of miR-34b on cell proliferation. It was also indicated that the expression of miR-34b in ALL patients may affect their response to early treatments.</description><subject>Acute lymphoblastic leukemia</subject><subject>Acute myeloid leukemia</subject><subject>Adolescent</subject><subject>Age</subject><subject>Blood</subject><subject>Bone marrow</subject><subject>Case-Control Studies</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Children & youth</subject><subject>Chromosomes</subject><subject>Clinical significance</subject><subject>CpG Islands</subject><subject>Dehydrogenases</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Down-Regulation</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Females</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Leukemic</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Infant</subject><subject>K562 Cells</subject><subject>Leukemia</subject><subject>leukemia cell proliferation</subject><subject>Leukemia in children</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Lymphatic leukemia</subject><subject>Lymphoma</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Myeloid leukemia</subject><subject>Ovarian cancer</subject><subject>Pathogenesis</subject><subject>Pediatrics</subject><subject>Polymerase chain reaction</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><subject>Prednisone</subject><subject>Promoter Regions, Genetic</subject><subject>Properties</subject><subject>RNA Interference</subject><subject>Standard deviation</subject><subject>Transfection</subject><subject>Tumor cell lines</subject><issn>1791-2997</issn><issn>1791-3004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</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><recordid>eNptkcuLFDEQxhtR3IcevUqDB_eSMa9JdY7D4AsGBdFzyKQrS9bupE26Yf3vTTPjiiJ1qKL41UdVfU3zgtGN6DR_M455wylTG9mBetRcMtCMCErl43PNtYaL5qqUO0rVlm_10-aCq04xJfllc9gPIQZnh7aE2xh8LaPDNvl2DC6nL592RMhji_dTxlJCim2I7YR9sHMOrrVumbEdcPmOY7DPmifeDgWfn_N18-3d26_7D-Tw-f3H_e5AnNzqmTjHPQXwqEXHJOMOJWoK2tcOB6cYML_14qhY3wmOTEtA8Jz2Sh47Ab24bm5OulNOPxYssxlDcTgMNmJaimEAuv6mXl7RV_-gd2nJsW5nmBZcgpIg_1C3dkATok9ztm4VNTspOyk5o6vW5j9Ujb4e71JEH2r_rwFyGqifLCWjN1MOo80_DaNmdc9U98zqnlndq_zL87LLccT-gf5tVwVen4Ay2diHPpUHpioRJggVhAOA-AUBI59I</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>CAO, LAN</creator><creator>WANG, NA</creator><creator>PAN, JIAN</creator><creator>HU, SHAOYAN</creator><creator>ZHAO, WENLI</creator><creator>HE, HAILONG</creator><creator>WANG, YI</creator><creator>GU, GUIXIONG</creator><creator>CHAI, YIHUAN</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20160301</creationdate><title>Clinical significance of microRNA-34b expression in pediatric acute leukemia</title><author>CAO, LAN ; WANG, NA ; PAN, JIAN ; HU, SHAOYAN ; ZHAO, WENLI ; HE, HAILONG ; WANG, YI ; GU, GUIXIONG ; CHAI, YIHUAN</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-cc2f077fe9381412ce4e9079ffe927c6171f5f3b61d832e1947e7f20d64b837d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Acute myeloid leukemia</topic><topic>Adolescent</topic><topic>Age</topic><topic>Blood</topic><topic>Bone marrow</topic><topic>Case-Control Studies</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Chemotherapy</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Children & youth</topic><topic>Chromosomes</topic><topic>Clinical significance</topic><topic>CpG Islands</topic><topic>Dehydrogenases</topic><topic>Deoxyribonucleic acid</topic><topic>Development and progression</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Down-Regulation</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Females</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Leukemic</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Infant</topic><topic>K562 Cells</topic><topic>Leukemia</topic><topic>leukemia cell proliferation</topic><topic>Leukemia in children</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Lymphatic leukemia</topic><topic>Lymphoma</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Myeloid leukemia</topic><topic>Ovarian cancer</topic><topic>Pathogenesis</topic><topic>Pediatrics</topic><topic>Polymerase chain reaction</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism</topic><topic>Prednisone</topic><topic>Promoter Regions, Genetic</topic><topic>Properties</topic><topic>RNA Interference</topic><topic>Standard deviation</topic><topic>Transfection</topic><topic>Tumor cell lines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CAO, LAN</creatorcontrib><creatorcontrib>WANG, NA</creatorcontrib><creatorcontrib>PAN, JIAN</creatorcontrib><creatorcontrib>HU, SHAOYAN</creatorcontrib><creatorcontrib>ZHAO, WENLI</creatorcontrib><creatorcontrib>HE, HAILONG</creatorcontrib><creatorcontrib>WANG, YI</creatorcontrib><creatorcontrib>GU, GUIXIONG</creatorcontrib><creatorcontrib>CHAI, YIHUAN</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular medicine reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CAO, LAN</au><au>WANG, NA</au><au>PAN, JIAN</au><au>HU, SHAOYAN</au><au>ZHAO, WENLI</au><au>HE, HAILONG</au><au>WANG, YI</au><au>GU, GUIXIONG</au><au>CHAI, YIHUAN</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical significance of microRNA-34b expression in pediatric acute leukemia</atitle><jtitle>Molecular medicine reports</jtitle><addtitle>Mol Med Rep</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>13</volume><issue>3</issue><spage>2777</spage><epage>2784</epage><pages>2777-2784</pages><issn>1791-2997</issn><eissn>1791-3004</eissn><abstract>The present study aimed to explore the function of miR-34b promoter methylation in cell proliferation in children's acute leukemia. Quantitative PCR and methylation-specific PCR were performed to measure the levels of miR-34b and its promoter methylation in normal cells, eight leukemia cell lines as well as primary leukemic cells isolated from patients newly diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed lymphocytic lymphoma. miR-34b levels in leukemia cell lines and primary leukemic cells were significantly lower than those in normal cells. The miR-34b promoter was found to be methylated in all leukemia cell lines, 24 of 31 ALL patients and 8 of 19 AML patients, but not in the 23 normal controls. miR-34b expression and methylation of its promoter were not associated with most clinical parameters assessed; however, miR-34b levels in prednisone-sensitive ALL were significantly different from those in insensitive ALL. A cell counting kit-8 assay showed that transfection of miR-34b mimics into K562 cells inhibited their proliferation. Furthermore, treatment with the demethylating agent 5-aza-2-deoxycytidine significantly enhanced miR-34b expression levels and decreased the methylation status of its promoter in HL-60 and K562 cells. In conclusion, the results of the present study indicated that in pediatric leukemia cells and leukemia cell lines, the expression of miR-34b is inhibited by methylation of its promoter, which impairs the restraining effects of miR-34b on cell proliferation. It was also indicated that the expression of miR-34b in ALL patients may affect their response to early treatments.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>26861642</pmid><doi>10.3892/mmr.2016.4876</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acute lymphoblastic leukemia Acute myeloid leukemia Adolescent Age Blood Bone marrow Case-Control Studies Cell growth Cell Line, Tumor Cell Proliferation Chemotherapy Child Child, Preschool Children Children & youth Chromosomes Clinical significance CpG Islands Dehydrogenases Deoxyribonucleic acid Development and progression DNA DNA Methylation Down-Regulation Epigenetics Female Females Gene expression Gene Expression Regulation, Leukemic Genetic aspects Health aspects HL-60 Cells Humans Infant K562 Cells Leukemia leukemia cell proliferation Leukemia in children Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - metabolism Lymphatic leukemia Lymphoma Male Medical prognosis Metastasis MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miRNA Myeloid leukemia Ovarian cancer Pathogenesis Pediatrics Polymerase chain reaction Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism Prednisone Promoter Regions, Genetic Properties RNA Interference Standard deviation Transfection Tumor cell lines |
| title | Clinical significance of microRNA-34b expression in pediatric acute leukemia |
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