MiR-146b-5p suppresses the malignancy of GSC/MSC fusion cells by targeting SMARCA5
Recent studies have confirmed that both cancer-associated bone marrow mesenchymal stem cells (BM-MSCs, MSCs) and glioma stem-like cells (GSCs) contribute to malignant progression of gliomas through their mutual interactions within the tumor microenvironment. However, the exact ways and relevant mech...
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| Veröffentlicht in: | Aging (Albany, NY.) NY.), 2020-07, Vol.12 (13), p.13647-13667 |
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| creator | Wang, Haiyang Tan, Liping Dong, Xuchen Liu, Liang Jiang, Qianqian Li, Haoran Shi, Jia Yang, Xuejun Dai, Xingliang Qian, Zhiyuan Dong, Jun |
| description | Recent studies have confirmed that both cancer-associated bone marrow mesenchymal stem cells (BM-MSCs, MSCs) and glioma stem-like cells (GSCs) contribute to malignant progression of gliomas through their mutual interactions within the tumor microenvironment. However, the exact ways and relevant mechanisms involved in the actions of GSCs and MSCs within the glioma microenvironment are not fully understood. Using a dual-color fluorescence tracing model, our studies revealed that GSCs are able to spontaneously fuse with MSCs, yielding GSC/MSC fusion cells, which exhibited markedly enhanced proliferation and invasiveness. MiR-146b-5p was downregulated in the GSC/MSC fusion cells, and its overexpression suppressed proliferation, migration and invasion by the fusion cells. SMARCA5, which is highly expressed in high-grade gliomas, was a direct downstream target of miR-146b-5p in the GSC/MSC fusion cells. miR-146b-5p inhibited SMARCA5 expression and inactivated a TGF-β pathway, thereby decreasing GSC/MSC fusion cell proliferation, migration and invasion. Collectively, these findings demonstrate that miR-146b-5p suppresses the malignant phenotype of GSC/MSC fusion cells in the glioma microenvironment by targeting a SMARCA5-regulated TGF-β pathway. |
| doi_str_mv | 10.18632/aging.103489 |
| format | Article |
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However, the exact ways and relevant mechanisms involved in the actions of GSCs and MSCs within the glioma microenvironment are not fully understood. Using a dual-color fluorescence tracing model, our studies revealed that GSCs are able to spontaneously fuse with MSCs, yielding GSC/MSC fusion cells, which exhibited markedly enhanced proliferation and invasiveness. MiR-146b-5p was downregulated in the GSC/MSC fusion cells, and its overexpression suppressed proliferation, migration and invasion by the fusion cells. SMARCA5, which is highly expressed in high-grade gliomas, was a direct downstream target of miR-146b-5p in the GSC/MSC fusion cells. miR-146b-5p inhibited SMARCA5 expression and inactivated a TGF-β pathway, thereby decreasing GSC/MSC fusion cell proliferation, migration and invasion. Collectively, these findings demonstrate that miR-146b-5p suppresses the malignant phenotype of GSC/MSC fusion cells in the glioma microenvironment by targeting a SMARCA5-regulated TGF-β pathway.</description><identifier>ISSN: 1945-4589</identifier><identifier>EISSN: 1945-4589</identifier><identifier>DOI: 10.18632/aging.103489</identifier><identifier>PMID: 32632040</identifier><language>eng</language><publisher>United States: Impact Journals</publisher><subject>Adenosine Triphosphatases - genetics ; Aged ; Astrocytes ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Cell Fusion ; Cell Line ; Cell Movement - genetics ; Cell Proliferation - genetics ; Chromosomal Proteins, Non-Histone - genetics ; Gene Expression Regulation, Neoplastic ; Glioblastoma - genetics ; Glioblastoma - pathology ; Humans ; Male ; Mesenchymal Stem Cells - pathology ; MicroRNAs - metabolism ; Neoplasm Invasiveness - genetics ; Neoplastic Stem Cells - pathology ; Primary Cell Culture ; Research Paper ; Signal Transduction - genetics ; Transforming Growth Factor beta - metabolism ; Tumor Cells, Cultured ; Tumor Microenvironment - genetics ; Xenograft Model Antitumor Assays</subject><ispartof>Aging (Albany, NY.), 2020-07, Vol.12 (13), p.13647-13667</ispartof><rights>Copyright © 2020 Wang et al.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-864d02b92f014fe1c7f59324d87de935fef43d6f00ae96a2c8bec4bb0a7ecac53</citedby><cites>FETCH-LOGICAL-c387t-864d02b92f014fe1c7f59324d87de935fef43d6f00ae96a2c8bec4bb0a7ecac53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377863/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377863/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32632040$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Haiyang</creatorcontrib><creatorcontrib>Tan, Liping</creatorcontrib><creatorcontrib>Dong, Xuchen</creatorcontrib><creatorcontrib>Liu, Liang</creatorcontrib><creatorcontrib>Jiang, Qianqian</creatorcontrib><creatorcontrib>Li, Haoran</creatorcontrib><creatorcontrib>Shi, Jia</creatorcontrib><creatorcontrib>Yang, Xuejun</creatorcontrib><creatorcontrib>Dai, Xingliang</creatorcontrib><creatorcontrib>Qian, Zhiyuan</creatorcontrib><creatorcontrib>Dong, Jun</creatorcontrib><title>MiR-146b-5p suppresses the malignancy of GSC/MSC fusion cells by targeting SMARCA5</title><title>Aging (Albany, NY.)</title><addtitle>Aging (Albany NY)</addtitle><description>Recent studies have confirmed that both cancer-associated bone marrow mesenchymal stem cells (BM-MSCs, MSCs) and glioma stem-like cells (GSCs) contribute to malignant progression of gliomas through their mutual interactions within the tumor microenvironment. However, the exact ways and relevant mechanisms involved in the actions of GSCs and MSCs within the glioma microenvironment are not fully understood. Using a dual-color fluorescence tracing model, our studies revealed that GSCs are able to spontaneously fuse with MSCs, yielding GSC/MSC fusion cells, which exhibited markedly enhanced proliferation and invasiveness. MiR-146b-5p was downregulated in the GSC/MSC fusion cells, and its overexpression suppressed proliferation, migration and invasion by the fusion cells. SMARCA5, which is highly expressed in high-grade gliomas, was a direct downstream target of miR-146b-5p in the GSC/MSC fusion cells. miR-146b-5p inhibited SMARCA5 expression and inactivated a TGF-β pathway, thereby decreasing GSC/MSC fusion cell proliferation, migration and invasion. Collectively, these findings demonstrate that miR-146b-5p suppresses the malignant phenotype of GSC/MSC fusion cells in the glioma microenvironment by targeting a SMARCA5-regulated TGF-β pathway.</description><subject>Adenosine Triphosphatases - genetics</subject><subject>Aged</subject><subject>Astrocytes</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - pathology</subject><subject>Cell Fusion</subject><subject>Cell Line</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - pathology</subject><subject>Humans</subject><subject>Male</subject><subject>Mesenchymal Stem Cells - pathology</subject><subject>MicroRNAs - metabolism</subject><subject>Neoplasm Invasiveness - genetics</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Primary Cell Culture</subject><subject>Research Paper</subject><subject>Signal Transduction - genetics</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Microenvironment - genetics</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1945-4589</issn><issn>1945-4589</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctOwzAQtBCIQuHIFfnIJa0d23lckKoIClIrpBbOluOsU6O8iBOk_j2hLVU57Uo7Ozs7g9AdJRMaBcyfqtxW-YQSxqP4DF3RmAuPiyg-P-lH6Nq5T0ICIXhwiUbMHzYJJ1dotbQrj_Ig9USDXd80LTgHDncbwKUqbF6pSm9xbfB8nUyX6wSb3tm6whqKwuF0izvV5tANGvB6OVslM3GDLowqHNwe6hh9PD-9Jy_e4m3-mswWnmZR2HlRwDPip7FvCOUGqA6NiJnPsyjMIGbCgOEsCwwhCuJA-TpKQfM0JSoErbRgY_S45236tIRMQ9W1qpBNa0vVbmWtrPw_qexG5vW3DFkYDtYNBA8Hgrb-6sF1srTu9y9VQd076XOfUhKKOBig3h6q29q5FszxDCVyl4Pc5SD3OQz4-1NtR_Sf8ewHlP-EQQ</recordid><startdate>20200706</startdate><enddate>20200706</enddate><creator>Wang, Haiyang</creator><creator>Tan, Liping</creator><creator>Dong, Xuchen</creator><creator>Liu, Liang</creator><creator>Jiang, Qianqian</creator><creator>Li, Haoran</creator><creator>Shi, Jia</creator><creator>Yang, Xuejun</creator><creator>Dai, Xingliang</creator><creator>Qian, Zhiyuan</creator><creator>Dong, Jun</creator><general>Impact Journals</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200706</creationdate><title>MiR-146b-5p suppresses the malignancy of GSC/MSC fusion cells by targeting SMARCA5</title><author>Wang, Haiyang ; Tan, Liping ; Dong, Xuchen ; Liu, Liang ; Jiang, Qianqian ; Li, Haoran ; Shi, Jia ; Yang, Xuejun ; Dai, Xingliang ; Qian, Zhiyuan ; Dong, Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-864d02b92f014fe1c7f59324d87de935fef43d6f00ae96a2c8bec4bb0a7ecac53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenosine Triphosphatases - genetics</topic><topic>Aged</topic><topic>Astrocytes</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - pathology</topic><topic>Cell Fusion</topic><topic>Cell Line</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Chromosomal Proteins, Non-Histone - genetics</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Glioblastoma - genetics</topic><topic>Glioblastoma - pathology</topic><topic>Humans</topic><topic>Male</topic><topic>Mesenchymal Stem Cells - pathology</topic><topic>MicroRNAs - metabolism</topic><topic>Neoplasm Invasiveness - genetics</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Primary Cell Culture</topic><topic>Research Paper</topic><topic>Signal Transduction - genetics</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Microenvironment - genetics</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Wang, Haiyang</creatorcontrib><creatorcontrib>Tan, Liping</creatorcontrib><creatorcontrib>Dong, Xuchen</creatorcontrib><creatorcontrib>Liu, Liang</creatorcontrib><creatorcontrib>Jiang, Qianqian</creatorcontrib><creatorcontrib>Li, Haoran</creatorcontrib><creatorcontrib>Shi, Jia</creatorcontrib><creatorcontrib>Yang, Xuejun</creatorcontrib><creatorcontrib>Dai, Xingliang</creatorcontrib><creatorcontrib>Qian, Zhiyuan</creatorcontrib><creatorcontrib>Dong, Jun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging (Albany, NY.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Haiyang</au><au>Tan, Liping</au><au>Dong, Xuchen</au><au>Liu, Liang</au><au>Jiang, Qianqian</au><au>Li, Haoran</au><au>Shi, Jia</au><au>Yang, Xuejun</au><au>Dai, Xingliang</au><au>Qian, Zhiyuan</au><au>Dong, Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MiR-146b-5p suppresses the malignancy of GSC/MSC fusion cells by targeting SMARCA5</atitle><jtitle>Aging (Albany, NY.)</jtitle><addtitle>Aging (Albany NY)</addtitle><date>2020-07-06</date><risdate>2020</risdate><volume>12</volume><issue>13</issue><spage>13647</spage><epage>13667</epage><pages>13647-13667</pages><issn>1945-4589</issn><eissn>1945-4589</eissn><abstract>Recent studies have confirmed that both cancer-associated bone marrow mesenchymal stem cells (BM-MSCs, MSCs) and glioma stem-like cells (GSCs) contribute to malignant progression of gliomas through their mutual interactions within the tumor microenvironment. However, the exact ways and relevant mechanisms involved in the actions of GSCs and MSCs within the glioma microenvironment are not fully understood. Using a dual-color fluorescence tracing model, our studies revealed that GSCs are able to spontaneously fuse with MSCs, yielding GSC/MSC fusion cells, which exhibited markedly enhanced proliferation and invasiveness. MiR-146b-5p was downregulated in the GSC/MSC fusion cells, and its overexpression suppressed proliferation, migration and invasion by the fusion cells. SMARCA5, which is highly expressed in high-grade gliomas, was a direct downstream target of miR-146b-5p in the GSC/MSC fusion cells. miR-146b-5p inhibited SMARCA5 expression and inactivated a TGF-β pathway, thereby decreasing GSC/MSC fusion cell proliferation, migration and invasion. Collectively, these findings demonstrate that miR-146b-5p suppresses the malignant phenotype of GSC/MSC fusion cells in the glioma microenvironment by targeting a SMARCA5-regulated TGF-β pathway.</abstract><cop>United States</cop><pub>Impact Journals</pub><pmid>32632040</pmid><doi>10.18632/aging.103489</doi><tpages>21</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Adenosine Triphosphatases - genetics Aged Astrocytes Brain Neoplasms - genetics Brain Neoplasms - pathology Cell Fusion Cell Line Cell Movement - genetics Cell Proliferation - genetics Chromosomal Proteins, Non-Histone - genetics Gene Expression Regulation, Neoplastic Glioblastoma - genetics Glioblastoma - pathology Humans Male Mesenchymal Stem Cells - pathology MicroRNAs - metabolism Neoplasm Invasiveness - genetics Neoplastic Stem Cells - pathology Primary Cell Culture Research Paper Signal Transduction - genetics Transforming Growth Factor beta - metabolism Tumor Cells, Cultured Tumor Microenvironment - genetics Xenograft Model Antitumor Assays |
| title | MiR-146b-5p suppresses the malignancy of GSC/MSC fusion cells by targeting SMARCA5 |
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