STUB1-SMYD2 Axis Regulates Drug Resistance in Glioma cells
SET and MYND domain-containing protein 2 (SMYD2) is an important epigenetic regulator that methylates histone and non-histone proteins. The study aimed to investigate the oncogenic role of SMYD2 in gliomas and explore its degradation mechanism induced by cisplatin. Tumor tissue microarray of 441 pat...
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| Veröffentlicht in: | Journal of molecular neuroscience 2022-09, Vol.72 (9), p.2030-2044 |
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| creator | Pan, Kailing Hu, Bin Wang, Lude Yuan, Jianlie Xu, Wenxia |
| description | SET and MYND domain-containing protein 2 (SMYD2) is an important epigenetic regulator that methylates histone and non-histone proteins. The study aimed to investigate the oncogenic role of SMYD2 in gliomas and explore its degradation mechanism induced by cisplatin. Tumor tissue microarray of 441 patients with glioma was collected for SMYD2 immunohistochemical staining. Kaplan–Meier survival curves were constructed using the overall survival values. mRNA-sequencing analysis was performed for understanding the downstream mechanisms mediated by SMYD2. The half-inhibitory concentrations (IC50) of temozolomide and cisplatin in AZ505-treated and control cells were calculated. The potential E3 ubiquitin ligase of SMYD2 was predicted in UbiBrowser and confirmed by a knockdown test. The effect of SMYD2 and its E3 ligase on apoptosis and migration of glioma cells was determined via cell-function assays. High SMYD2 expression correlated with a high WHO stage (
P
= 0.004) and a low survival probability (
P
= 0.012). The inhibition of SMYD2 suppressed the process of
epithelial to mesenchymal transition
(EMT) by downregulating the expression of Collagen 1A1 (COL1A1). AZ505 treatment significantly increased the drug sensitivity of glioma cells. SMYD2 expression was markedly reduced by cisplatin treatment via STIP1 Homology And U-Box Containing Protein 1 (STUB1)-mediated degradation. The knockdown of STUB1 could partly reverse the cell function impairment induced by cisplatin. Our findings suggested that SMYD2 could be a potential drug target for the treatment of gliomas, and STUB1-mediated degradation of SMYD2 plays an important role in reversing chemotherapy resistance in patients with gliomas. |
| doi_str_mv | 10.1007/s12031-022-02051-5 |
| format | Article |
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P
= 0.004) and a low survival probability (
P
= 0.012). The inhibition of SMYD2 suppressed the process of
epithelial to mesenchymal transition
(EMT) by downregulating the expression of Collagen 1A1 (COL1A1). AZ505 treatment significantly increased the drug sensitivity of glioma cells. SMYD2 expression was markedly reduced by cisplatin treatment via STIP1 Homology And U-Box Containing Protein 1 (STUB1)-mediated degradation. The knockdown of STUB1 could partly reverse the cell function impairment induced by cisplatin. Our findings suggested that SMYD2 could be a potential drug target for the treatment of gliomas, and STUB1-mediated degradation of SMYD2 plays an important role in reversing chemotherapy resistance in patients with gliomas.</description><identifier>ISSN: 0895-8696</identifier><identifier>EISSN: 1559-1166</identifier><identifier>DOI: 10.1007/s12031-022-02051-5</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Antibodies ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Brain cancer ; Brain tumors ; Cell Biology ; Cell growth ; Cell migration ; Chemoresistance ; Chemotherapy ; Cisplatin ; Collagen ; Collagen (type I) ; Degradation ; Drug resistance ; Epigenetics ; Gene sequencing ; Glioma ; Glioma cells ; Histones ; Homology ; Medical prognosis ; Mesenchyme ; mRNA ; Neurochemistry ; Neurology ; Neurosciences ; Patients ; Proteins ; Proteomics ; Sequence analysis ; Survival ; Temozolomide ; Therapeutic targets ; Ubiquitin ; Ubiquitin-protein ligase</subject><ispartof>Journal of molecular neuroscience, 2022-09, Vol.72 (9), p.2030-2044</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c282t-465f67a9630c1acd49d7f23d6ad6fba268b2866d6356e12bbc1307c9a1c64d1a3</citedby><cites>FETCH-LOGICAL-c282t-465f67a9630c1acd49d7f23d6ad6fba268b2866d6356e12bbc1307c9a1c64d1a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12031-022-02051-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12031-022-02051-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids></links><search><creatorcontrib>Pan, Kailing</creatorcontrib><creatorcontrib>Hu, Bin</creatorcontrib><creatorcontrib>Wang, Lude</creatorcontrib><creatorcontrib>Yuan, Jianlie</creatorcontrib><creatorcontrib>Xu, Wenxia</creatorcontrib><title>STUB1-SMYD2 Axis Regulates Drug Resistance in Glioma cells</title><title>Journal of molecular neuroscience</title><addtitle>J Mol Neurosci</addtitle><description>SET and MYND domain-containing protein 2 (SMYD2) is an important epigenetic regulator that methylates histone and non-histone proteins. The study aimed to investigate the oncogenic role of SMYD2 in gliomas and explore its degradation mechanism induced by cisplatin. Tumor tissue microarray of 441 patients with glioma was collected for SMYD2 immunohistochemical staining. Kaplan–Meier survival curves were constructed using the overall survival values. mRNA-sequencing analysis was performed for understanding the downstream mechanisms mediated by SMYD2. The half-inhibitory concentrations (IC50) of temozolomide and cisplatin in AZ505-treated and control cells were calculated. The potential E3 ubiquitin ligase of SMYD2 was predicted in UbiBrowser and confirmed by a knockdown test. The effect of SMYD2 and its E3 ligase on apoptosis and migration of glioma cells was determined via cell-function assays. High SMYD2 expression correlated with a high WHO stage (
P
= 0.004) and a low survival probability (
P
= 0.012). The inhibition of SMYD2 suppressed the process of
epithelial to mesenchymal transition
(EMT) by downregulating the expression of Collagen 1A1 (COL1A1). AZ505 treatment significantly increased the drug sensitivity of glioma cells. SMYD2 expression was markedly reduced by cisplatin treatment via STIP1 Homology And U-Box Containing Protein 1 (STUB1)-mediated degradation. The knockdown of STUB1 could partly reverse the cell function impairment induced by cisplatin. Our findings suggested that SMYD2 could be a potential drug target for the treatment of gliomas, and STUB1-mediated degradation of SMYD2 plays an important role in reversing chemotherapy resistance in patients with gliomas.</description><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Brain cancer</subject><subject>Brain tumors</subject><subject>Cell Biology</subject><subject>Cell growth</subject><subject>Cell migration</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Collagen</subject><subject>Collagen (type I)</subject><subject>Degradation</subject><subject>Drug resistance</subject><subject>Epigenetics</subject><subject>Gene sequencing</subject><subject>Glioma</subject><subject>Glioma cells</subject><subject>Histones</subject><subject>Homology</subject><subject>Medical prognosis</subject><subject>Mesenchyme</subject><subject>mRNA</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Patients</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Sequence analysis</subject><subject>Survival</subject><subject>Temozolomide</subject><subject>Therapeutic targets</subject><subject>Ubiquitin</subject><subject>Ubiquitin-protein ligase</subject><issn>0895-8696</issn><issn>1559-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kEFLwzAUx4MoOKdfwFPBi5dqXtK8Nt7mplNQBLcdPIU0TUdH186kBf32ZlYQPHh4PB78_n8eP0LOgV4Bpem1B0Y5xJSxMFRALA7ICISQMQDiIRnRTIo4Q4nH5MT7DaUMEshG5GaxXN1CvHh-m7Fo8lH56NWu-1p31kcz16_D6Svf6cbYqGqieV21Wx0ZW9f-lByVuvb27GePyer-bjl9iJ9e5o_TyVNsWMa6OEFRYqolcmpAmyKRRVoyXqAusMw1wyxnGWKBXKAFlucGOE2N1GAwKUDzMbkceneufe-t79S28vsPdGPb3iuGUkqRMmQBvfiDbtreNeE7xVKaCAoceKDYQBnXeu9sqXau2mr3qYCqvU416FRBp_rWqUQI8SHkA9ysrfut_if1BdlKdKE</recordid><startdate>20220901</startdate><enddate>20220901</enddate><creator>Pan, Kailing</creator><creator>Hu, Bin</creator><creator>Wang, Lude</creator><creator>Yuan, Jianlie</creator><creator>Xu, Wenxia</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20220901</creationdate><title>STUB1-SMYD2 Axis Regulates Drug Resistance in Glioma cells</title><author>Pan, Kailing ; Hu, Bin ; Wang, Lude ; Yuan, Jianlie ; Xu, Wenxia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c282t-465f67a9630c1acd49d7f23d6ad6fba268b2866d6356e12bbc1307c9a1c64d1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Brain cancer</topic><topic>Brain tumors</topic><topic>Cell Biology</topic><topic>Cell growth</topic><topic>Cell migration</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Collagen</topic><topic>Collagen (type I)</topic><topic>Degradation</topic><topic>Drug resistance</topic><topic>Epigenetics</topic><topic>Gene sequencing</topic><topic>Glioma</topic><topic>Glioma cells</topic><topic>Histones</topic><topic>Homology</topic><topic>Medical prognosis</topic><topic>Mesenchyme</topic><topic>mRNA</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Patients</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Sequence analysis</topic><topic>Survival</topic><topic>Temozolomide</topic><topic>Therapeutic targets</topic><topic>Ubiquitin</topic><topic>Ubiquitin-protein ligase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pan, Kailing</creatorcontrib><creatorcontrib>Hu, Bin</creatorcontrib><creatorcontrib>Wang, Lude</creatorcontrib><creatorcontrib>Yuan, Jianlie</creatorcontrib><creatorcontrib>Xu, Wenxia</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pan, Kailing</au><au>Hu, Bin</au><au>Wang, Lude</au><au>Yuan, Jianlie</au><au>Xu, Wenxia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>STUB1-SMYD2 Axis Regulates Drug Resistance in Glioma cells</atitle><jtitle>Journal of molecular neuroscience</jtitle><stitle>J Mol Neurosci</stitle><date>2022-09-01</date><risdate>2022</risdate><volume>72</volume><issue>9</issue><spage>2030</spage><epage>2044</epage><pages>2030-2044</pages><issn>0895-8696</issn><eissn>1559-1166</eissn><abstract>SET and MYND domain-containing protein 2 (SMYD2) is an important epigenetic regulator that methylates histone and non-histone proteins. The study aimed to investigate the oncogenic role of SMYD2 in gliomas and explore its degradation mechanism induced by cisplatin. Tumor tissue microarray of 441 patients with glioma was collected for SMYD2 immunohistochemical staining. Kaplan–Meier survival curves were constructed using the overall survival values. mRNA-sequencing analysis was performed for understanding the downstream mechanisms mediated by SMYD2. The half-inhibitory concentrations (IC50) of temozolomide and cisplatin in AZ505-treated and control cells were calculated. The potential E3 ubiquitin ligase of SMYD2 was predicted in UbiBrowser and confirmed by a knockdown test. The effect of SMYD2 and its E3 ligase on apoptosis and migration of glioma cells was determined via cell-function assays. High SMYD2 expression correlated with a high WHO stage (
P
= 0.004) and a low survival probability (
P
= 0.012). The inhibition of SMYD2 suppressed the process of
epithelial to mesenchymal transition
(EMT) by downregulating the expression of Collagen 1A1 (COL1A1). AZ505 treatment significantly increased the drug sensitivity of glioma cells. SMYD2 expression was markedly reduced by cisplatin treatment via STIP1 Homology And U-Box Containing Protein 1 (STUB1)-mediated degradation. The knockdown of STUB1 could partly reverse the cell function impairment induced by cisplatin. Our findings suggested that SMYD2 could be a potential drug target for the treatment of gliomas, and STUB1-mediated degradation of SMYD2 plays an important role in reversing chemotherapy resistance in patients with gliomas.</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s12031-022-02051-5</doi><tpages>15</tpages></addata></record> |
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| subjects | Antibodies Apoptosis Biomedical and Life Sciences Biomedicine Biotechnology Brain cancer Brain tumors Cell Biology Cell growth Cell migration Chemoresistance Chemotherapy Cisplatin Collagen Collagen (type I) Degradation Drug resistance Epigenetics Gene sequencing Glioma Glioma cells Histones Homology Medical prognosis Mesenchyme mRNA Neurochemistry Neurology Neurosciences Patients Proteins Proteomics Sequence analysis Survival Temozolomide Therapeutic targets Ubiquitin Ubiquitin-protein ligase |
| title | STUB1-SMYD2 Axis Regulates Drug Resistance in Glioma cells |
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