Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR-218/Bmi1 pathway
In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigen...
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| description | In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo. The untreated cell lines served as control. The HK2 expression in (a) lentivirus-infected, miR-218 overexpressing and (b) shRNA mediated Bmi1 silenced U87 and U251 glioma cell lines were quantified. Luciferase reporter assay, qRT-PCR analysis and WB were employed as required. The HK2 expression was significantly increased in glioma tissues comparing with the non neoplastic brain tissues and was positively correlated with the glioma grade. Silencing HK2 in glioma cell lines significantly decreased their proliferation, migration, invasion and tumorigenic abilities. Although, overexpression of miR-218 significantly downregulated the HK2 expression, luciferase reporter assay failed to show HK2 as the direct target of miR-218. A direct correlation, however, was observed between HK2 and Bmi-1, the direct target of miR-218. Taken together, our findings confirmed the tumorigenic activity of HK2 in glioma, and the involvement of the miR218/Bmi1 pathway in the regulation of its expression. |
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The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo. The untreated cell lines served as control. The HK2 expression in (a) lentivirus-infected, miR-218 overexpressing and (b) shRNA mediated Bmi1 silenced U87 and U251 glioma cell lines were quantified. Luciferase reporter assay, qRT-PCR analysis and WB were employed as required. The HK2 expression was significantly increased in glioma tissues comparing with the non neoplastic brain tissues and was positively correlated with the glioma grade. Silencing HK2 in glioma cell lines significantly decreased their proliferation, migration, invasion and tumorigenic abilities. Although, overexpression of miR-218 significantly downregulated the HK2 expression, luciferase reporter assay failed to show HK2 as the direct target of miR-218. A direct correlation, however, was observed between HK2 and Bmi-1, the direct target of miR-218. Taken together, our findings confirmed the tumorigenic activity of HK2 in glioma, and the involvement of the miR218/Bmi1 pathway in the regulation of its expression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0189353</identifier><identifier>PMID: 29220380</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Analysis ; Apoptosis ; Biology and Life Sciences ; Biotechnology ; Bmi protein ; Brain ; Brain cancer ; Brain Neoplasms - enzymology ; Brain Neoplasms - metabolism ; Brain research ; Brain tumors ; Cancer therapies ; Cell Line, Tumor ; Chemotherapy ; Development and progression ; Down-Regulation ; Enzymes ; Female ; Gene Silencing ; Genes ; Glioma ; Glioma - enzymology ; Glioma - metabolism ; Glioma cells ; Gliomas ; Glucose metabolism ; Glycolysis ; Health aspects ; Hexokinase ; Hexokinase - genetics ; Hexokinase - metabolism ; Humans ; Invasiveness ; Laboratories ; Lung cancer ; Male ; Medical research ; Medicine and Health Sciences ; Metabolism ; MicroRNA ; MicroRNAs ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; Mitochondria ; Mitogen-Activated Protein Kinase 7 - metabolism ; Nervous system ; Neurosurgery ; Oncology ; Quality ; Radiation therapy ; Research and Analysis Methods ; Surgery ; Tissues ; Tumorigenesis ; Tumors</subject><ispartof>PloS one, 2017-12, Vol.12 (12), p.e0189353-e0189353</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Liu et al 2017 Liu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c659t-598f33524130a8bb81fdcfe0cc2275eb2771bed3afa884da50772672a29c50473</citedby><cites>FETCH-LOGICAL-c659t-598f33524130a8bb81fdcfe0cc2275eb2771bed3afa884da50772672a29c50473</cites><orcidid>0000-0002-8970-7314</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722312/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722312/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29220380$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Hui</creatorcontrib><creatorcontrib>Liu, Nan</creatorcontrib><creatorcontrib>Cheng, Yingduan</creatorcontrib><creatorcontrib>Jin, Weilin</creatorcontrib><creatorcontrib>Zhang, Pengxing</creatorcontrib><creatorcontrib>Wang, Xin</creatorcontrib><creatorcontrib>Yang, Hongwei</creatorcontrib><creatorcontrib>Xu, Xiaoshan</creatorcontrib><creatorcontrib>Wang, Zhen</creatorcontrib><creatorcontrib>Tu, Yanyang</creatorcontrib><title>Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR-218/Bmi1 pathway</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo. The untreated cell lines served as control. The HK2 expression in (a) lentivirus-infected, miR-218 overexpressing and (b) shRNA mediated Bmi1 silenced U87 and U251 glioma cell lines were quantified. Luciferase reporter assay, qRT-PCR analysis and WB were employed as required. The HK2 expression was significantly increased in glioma tissues comparing with the non neoplastic brain tissues and was positively correlated with the glioma grade. Silencing HK2 in glioma cell lines significantly decreased their proliferation, migration, invasion and tumorigenic abilities. Although, overexpression of miR-218 significantly downregulated the HK2 expression, luciferase reporter assay failed to show HK2 as the direct target of miR-218. A direct correlation, however, was observed between HK2 and Bmi-1, the direct target of miR-218. Taken together, our findings confirmed the tumorigenic activity of HK2 in glioma, and the involvement of the miR218/Bmi1 pathway in the regulation of its expression.</description><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Biology and Life Sciences</subject><subject>Biotechnology</subject><subject>Bmi protein</subject><subject>Brain</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - enzymology</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain research</subject><subject>Brain tumors</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Development and progression</subject><subject>Down-Regulation</subject><subject>Enzymes</subject><subject>Female</subject><subject>Gene Silencing</subject><subject>Genes</subject><subject>Glioma</subject><subject>Glioma - enzymology</subject><subject>Glioma - metabolism</subject><subject>Glioma cells</subject><subject>Gliomas</subject><subject>Glucose metabolism</subject><subject>Glycolysis</subject><subject>Health aspects</subject><subject>Hexokinase</subject><subject>Hexokinase - genetics</subject><subject>Hexokinase - metabolism</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Laboratories</subject><subject>Lung cancer</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Mitochondria</subject><subject>Mitogen-Activated Protein Kinase 7 - metabolism</subject><subject>Nervous system</subject><subject>Neurosurgery</subject><subject>Oncology</subject><subject>Quality</subject><subject>Radiation therapy</subject><subject>Research and Analysis Methods</subject><subject>Surgery</subject><subject>Tissues</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1v1DAUjBCIlsI_QGCJS5G6W_s5ju0LUqmAraiEhODCxXKcl10vSby1E8r-e7LdtGpR5YOt8cy8D02WvWZ0zrhkp-swxM42803ocE6Z0lzwJ9kh0xxmBVD-9N77IHuR0ppSwVVRPM8OQMOIKnqY_Vrg3_DbdzYhAXK8-ArvT0i_QtIPbYhkE0MbeozEd2TZ-NDaE-ITqcJ1F3E5NLbHipRb0vrvM2Dq9GPrGdnYfnVtty-zZ7VtEr6a7qPs5-dPP84Xs8tvXy7Ozy5nrhC6nwmtas4F5IxTq8pSsbpyNVLnAKTAEqRkJVbc1lapvLKCSgmFBAvaCZpLfpS93ftumpDMtJZkmJa5kIqxHeNiz6iCXZtN9K2NWxOsNzdAiEtjY-9dg0YytJXTmjOmc-eoqgpwpQObAyDWevT6MFUbyhYrh10fbfPA9OFP51dmGf4YIQE4g9HgeDKI4WrA1JvWJ4dNYzsMw03fgnJgkI_Ud_9RH59uYi3tOIDv6jDWdTtTcyaY1FLnoEbW_BHWeCpsvRszVPsRfyDI9wIXQ0oR67sZGTW7BN42Y3YJNFMCR9mb-_u5E91Gjv8D29fV9Q</recordid><startdate>20171208</startdate><enddate>20171208</enddate><creator>Liu, Hui</creator><creator>Liu, Nan</creator><creator>Cheng, Yingduan</creator><creator>Jin, Weilin</creator><creator>Zhang, Pengxing</creator><creator>Wang, Xin</creator><creator>Yang, Hongwei</creator><creator>Xu, Xiaoshan</creator><creator>Wang, Zhen</creator><creator>Tu, Yanyang</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>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>AEUYN</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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8970-7314</orcidid></search><sort><creationdate>20171208</creationdate><title>Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR-218/Bmi1 pathway</title><author>Liu, Hui ; Liu, Nan ; Cheng, Yingduan ; Jin, Weilin ; Zhang, Pengxing ; Wang, Xin ; Yang, Hongwei ; Xu, Xiaoshan ; Wang, Zhen ; Tu, Yanyang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c659t-598f33524130a8bb81fdcfe0cc2275eb2771bed3afa884da50772672a29c50473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Analysis</topic><topic>Apoptosis</topic><topic>Biology and Life Sciences</topic><topic>Biotechnology</topic><topic>Bmi protein</topic><topic>Brain</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - enzymology</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain research</topic><topic>Brain tumors</topic><topic>Cancer therapies</topic><topic>Cell Line, Tumor</topic><topic>Chemotherapy</topic><topic>Development and progression</topic><topic>Down-Regulation</topic><topic>Enzymes</topic><topic>Female</topic><topic>Gene Silencing</topic><topic>Genes</topic><topic>Glioma</topic><topic>Glioma - enzymology</topic><topic>Glioma - metabolism</topic><topic>Glioma cells</topic><topic>Gliomas</topic><topic>Glucose metabolism</topic><topic>Glycolysis</topic><topic>Health aspects</topic><topic>Hexokinase</topic><topic>Hexokinase - genetics</topic><topic>Hexokinase - metabolism</topic><topic>Humans</topic><topic>Invasiveness</topic><topic>Laboratories</topic><topic>Lung cancer</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Mitochondria</topic><topic>Mitogen-Activated Protein Kinase 7 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Hui</au><au>Liu, Nan</au><au>Cheng, Yingduan</au><au>Jin, Weilin</au><au>Zhang, Pengxing</au><au>Wang, Xin</au><au>Yang, Hongwei</au><au>Xu, Xiaoshan</au><au>Wang, Zhen</au><au>Tu, Yanyang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR-218/Bmi1 pathway</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-12-08</date><risdate>2017</risdate><volume>12</volume><issue>12</issue><spage>e0189353</spage><epage>e0189353</epage><pages>e0189353-e0189353</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo. The untreated cell lines served as control. The HK2 expression in (a) lentivirus-infected, miR-218 overexpressing and (b) shRNA mediated Bmi1 silenced U87 and U251 glioma cell lines were quantified. Luciferase reporter assay, qRT-PCR analysis and WB were employed as required. The HK2 expression was significantly increased in glioma tissues comparing with the non neoplastic brain tissues and was positively correlated with the glioma grade. Silencing HK2 in glioma cell lines significantly decreased their proliferation, migration, invasion and tumorigenic abilities. Although, overexpression of miR-218 significantly downregulated the HK2 expression, luciferase reporter assay failed to show HK2 as the direct target of miR-218. A direct correlation, however, was observed between HK2 and Bmi-1, the direct target of miR-218. Taken together, our findings confirmed the tumorigenic activity of HK2 in glioma, and the involvement of the miR218/Bmi1 pathway in the regulation of its expression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29220380</pmid><doi>10.1371/journal.pone.0189353</doi><orcidid>https://orcid.org/0000-0002-8970-7314</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Aged Analysis Apoptosis Biology and Life Sciences Biotechnology Bmi protein Brain Brain cancer Brain Neoplasms - enzymology Brain Neoplasms - metabolism Brain research Brain tumors Cancer therapies Cell Line, Tumor Chemotherapy Development and progression Down-Regulation Enzymes Female Gene Silencing Genes Glioma Glioma - enzymology Glioma - metabolism Glioma cells Gliomas Glucose metabolism Glycolysis Health aspects Hexokinase Hexokinase - genetics Hexokinase - metabolism Humans Invasiveness Laboratories Lung cancer Male Medical research Medicine and Health Sciences Metabolism MicroRNA MicroRNAs MicroRNAs - metabolism Middle Aged miRNA Mitochondria Mitogen-Activated Protein Kinase 7 - metabolism Nervous system Neurosurgery Oncology Quality Radiation therapy Research and Analysis Methods Surgery Tissues Tumorigenesis Tumors |
| title | Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR-218/Bmi1 pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T22%3A50%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hexokinase%202%20(HK2),%20the%20tumor%20promoter%20in%20glioma,%20is%20downregulated%20by%20miR-218/Bmi1%20pathway&rft.jtitle=PloS%20one&rft.au=Liu,%20Hui&rft.date=2017-12-08&rft.volume=12&rft.issue=12&rft.spage=e0189353&rft.epage=e0189353&rft.pages=e0189353-e0189353&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0189353&rft_dat=%3Cgale_plos_%3EA517979428%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1974578117&rft_id=info:pmid/29220380&rft_galeid=A517979428&rft_doaj_id=oai_doaj_org_article_71eadc9931194cc08d62cbc2a422eef9&rfr_iscdi=true |