LncRNA H19 overexpression induces bortezomib resistance in multiple myeloma by targeting MCL-1 via miR-29b-3p
Radiotherapy, chemotherapy, autologous/allogeneic stem cell transplantation, and targeted drug therapy are currently available therapeutic options for multiple myeloma (MM), but the clinical outcome remains unsatisfactory owing to frequent occurrence of drug resistance. Anti apoptosis is one of the...
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| Veröffentlicht in: | Cell death & disease 2019-02, Vol.10 (2), p.106, Article 106 |
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| creator | Pan, Yafang Zhang, Yu Liu, Wenwen Huang, Yan Shen, Xianjuan Jing, Rongrong Pu, Jiang Wang, Xudong Ju, Shaoqing Cong, Hui Chen, Hongmei |
| description | Radiotherapy, chemotherapy, autologous/allogeneic stem cell transplantation, and targeted drug therapy are currently available therapeutic options for multiple myeloma (MM), but the clinical outcome remains unsatisfactory owing to frequent occurrence of drug resistance. Anti apoptosis is one of the main mechanisms to mediate drug resistance. Studies have shown that MCL-1 plays a key role in the growth of cancer cells “escaping” drug attacks, but the underlying mechanism remains unclear. Our previous study demonstrated that lncRNA H19 was highly expressed in the serum of MM patients. Bioinformatics predicts that miR-29b-3p is the downstream target gene, and MCL-1 is the downstream target protein of miR-29b-3p. Therefore, we speculated that MCL-1 may be involved in the occurrence of drug resistance through epigenetics. On the basis of these previous findings, the present study was intended to explore the biological function of H19, interactions between the downstream target genes, and the effect of H19 on BTZ resistance of myeloma cells. In addition, in vivo experiments we have also confirmed that H19 promoted tumor growth and may develop resistance to bortezomib partly. It was found that H19 reduced cell sensitivity to the chemotherapeutic drug BTZ by working as a miRNA sponge to inhibit the expression of miR-29b-3p, enhance MCL-1 transcriptional translation and inhibit apoptosis. These findings may help gain insights into the molecular mechanism of acquired BTZ resistance and develop new drug targets for the clinical treatment of MM. |
| doi_str_mv | 10.1038/s41419-018-1219-0 |
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Anti apoptosis is one of the main mechanisms to mediate drug resistance. Studies have shown that MCL-1 plays a key role in the growth of cancer cells “escaping” drug attacks, but the underlying mechanism remains unclear. Our previous study demonstrated that lncRNA H19 was highly expressed in the serum of MM patients. Bioinformatics predicts that miR-29b-3p is the downstream target gene, and MCL-1 is the downstream target protein of miR-29b-3p. Therefore, we speculated that MCL-1 may be involved in the occurrence of drug resistance through epigenetics. On the basis of these previous findings, the present study was intended to explore the biological function of H19, interactions between the downstream target genes, and the effect of H19 on BTZ resistance of myeloma cells. In addition, in vivo experiments we have also confirmed that H19 promoted tumor growth and may develop resistance to bortezomib partly. It was found that H19 reduced cell sensitivity to the chemotherapeutic drug BTZ by working as a miRNA sponge to inhibit the expression of miR-29b-3p, enhance MCL-1 transcriptional translation and inhibit apoptosis. These findings may help gain insights into the molecular mechanism of acquired BTZ resistance and develop new drug targets for the clinical treatment of MM.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-018-1219-0</identifier><identifier>PMID: 30728351</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/2 ; 13/31 ; 14/32 ; 38/77 ; 631/67 ; 692/53 ; Antibodies ; Apoptosis ; Autografts ; Biochemistry ; Bioinformatics ; Biomedical and Life Sciences ; Bortezomib ; Cancer ; Cell Biology ; Cell Culture ; Chemotherapy ; Drug resistance ; Drug therapy ; Epigenetics ; Immunology ; Inhibitor drugs ; Life Sciences ; Mcl-1 protein ; miRNA ; Multiple myeloma ; Radiation therapy ; Stem cell transplantation ; Targeted cancer therapy ; Transcription</subject><ispartof>Cell death & disease, 2019-02, Vol.10 (2), p.106, Article 106</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-ba2df87dc5686fc7ad1a9d4c8f11ab5488adaab7d1a305e918a2d4bbf9a970003</citedby><cites>FETCH-LOGICAL-c470t-ba2df87dc5686fc7ad1a9d4c8f11ab5488adaab7d1a305e918a2d4bbf9a970003</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/PMC6365572/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365572/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51554,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30728351$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pan, Yafang</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>Liu, Wenwen</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>Shen, Xianjuan</creatorcontrib><creatorcontrib>Jing, Rongrong</creatorcontrib><creatorcontrib>Pu, Jiang</creatorcontrib><creatorcontrib>Wang, Xudong</creatorcontrib><creatorcontrib>Ju, Shaoqing</creatorcontrib><creatorcontrib>Cong, Hui</creatorcontrib><creatorcontrib>Chen, Hongmei</creatorcontrib><title>LncRNA H19 overexpression induces bortezomib resistance in multiple myeloma by targeting MCL-1 via miR-29b-3p</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Radiotherapy, chemotherapy, autologous/allogeneic stem cell transplantation, and targeted drug therapy are currently available therapeutic options for multiple myeloma (MM), but the clinical outcome remains unsatisfactory owing to frequent occurrence of drug resistance. Anti apoptosis is one of the main mechanisms to mediate drug resistance. Studies have shown that MCL-1 plays a key role in the growth of cancer cells “escaping” drug attacks, but the underlying mechanism remains unclear. Our previous study demonstrated that lncRNA H19 was highly expressed in the serum of MM patients. Bioinformatics predicts that miR-29b-3p is the downstream target gene, and MCL-1 is the downstream target protein of miR-29b-3p. Therefore, we speculated that MCL-1 may be involved in the occurrence of drug resistance through epigenetics. On the basis of these previous findings, the present study was intended to explore the biological function of H19, interactions between the downstream target genes, and the effect of H19 on BTZ resistance of myeloma cells. In addition, in vivo experiments we have also confirmed that H19 promoted tumor growth and may develop resistance to bortezomib partly. It was found that H19 reduced cell sensitivity to the chemotherapeutic drug BTZ by working as a miRNA sponge to inhibit the expression of miR-29b-3p, enhance MCL-1 transcriptional translation and inhibit apoptosis. These findings may help gain insights into the molecular mechanism of acquired BTZ resistance and develop new drug targets for the clinical treatment of MM.</description><subject>13/2</subject><subject>13/31</subject><subject>14/32</subject><subject>38/77</subject><subject>631/67</subject><subject>692/53</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Autografts</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Biomedical and Life Sciences</subject><subject>Bortezomib</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Chemotherapy</subject><subject>Drug resistance</subject><subject>Drug therapy</subject><subject>Epigenetics</subject><subject>Immunology</subject><subject>Inhibitor drugs</subject><subject>Life Sciences</subject><subject>Mcl-1 protein</subject><subject>miRNA</subject><subject>Multiple myeloma</subject><subject>Radiation therapy</subject><subject>Stem cell transplantation</subject><subject>Targeted cancer therapy</subject><subject>Transcription</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1UcFu1DAQtRAVrdp-ABdkibPBYyexc0GqVkCRFipV5WzZjrO4SuxgJ6suX4-jLaUc8MWjeW_evNFD6DXQd0C5fJ8rqKAlFCQBthYv0BmjFZBKyvbls_oUXeZ8T8vjnLK6eYVOORVM8hrO0LgN9vbbFb6GFse9S-5hSi5nHwP2oVusy9jENLtfcfQGF8jnWQfrCorHZZj9NDg8HtwQR43NAc867dzsww5_3WwJ4L3XePS3hLWG8OkCnfR6yO7y8T9H3z99vNtck-3N5y-bqy2xlaAzMZp1vRSdrRvZ9FboDnTbVVb2ANrU5SjdaW1EaXNauxZkGaiM6VvdivXOc_ThqDstZnSddWFOelBT8qNOBxW1V_8iwf9Qu7hXDW_qWrAi8PZRIMWfi8uzuo9LCsWzYiAaQRvOoLDgyLIp5pxc_7QBqFpDUseQVAlJrSGp1dqb59aeJv5EUgjsSMgFCjuX_q7-v-pvSYed5g</recordid><startdate>20190206</startdate><enddate>20190206</enddate><creator>Pan, Yafang</creator><creator>Zhang, Yu</creator><creator>Liu, Wenwen</creator><creator>Huang, Yan</creator><creator>Shen, Xianjuan</creator><creator>Jing, Rongrong</creator><creator>Pu, Jiang</creator><creator>Wang, Xudong</creator><creator>Ju, Shaoqing</creator><creator>Cong, Hui</creator><creator>Chen, Hongmei</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</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>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20190206</creationdate><title>LncRNA H19 overexpression induces bortezomib resistance in multiple myeloma by targeting MCL-1 via miR-29b-3p</title><author>Pan, Yafang ; Zhang, Yu ; Liu, Wenwen ; Huang, Yan ; Shen, Xianjuan ; Jing, Rongrong ; Pu, Jiang ; Wang, Xudong ; Ju, Shaoqing ; Cong, Hui ; Chen, Hongmei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-ba2df87dc5686fc7ad1a9d4c8f11ab5488adaab7d1a305e918a2d4bbf9a970003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/2</topic><topic>13/31</topic><topic>14/32</topic><topic>38/77</topic><topic>631/67</topic><topic>692/53</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Autografts</topic><topic>Biochemistry</topic><topic>Bioinformatics</topic><topic>Biomedical and Life Sciences</topic><topic>Bortezomib</topic><topic>Cancer</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Chemotherapy</topic><topic>Drug resistance</topic><topic>Drug therapy</topic><topic>Epigenetics</topic><topic>Immunology</topic><topic>Inhibitor drugs</topic><topic>Life Sciences</topic><topic>Mcl-1 protein</topic><topic>miRNA</topic><topic>Multiple myeloma</topic><topic>Radiation therapy</topic><topic>Stem cell transplantation</topic><topic>Targeted cancer therapy</topic><topic>Transcription</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pan, Yafang</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>Liu, Wenwen</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>Shen, Xianjuan</creatorcontrib><creatorcontrib>Jing, Rongrong</creatorcontrib><creatorcontrib>Pu, Jiang</creatorcontrib><creatorcontrib>Wang, Xudong</creatorcontrib><creatorcontrib>Ju, Shaoqing</creatorcontrib><creatorcontrib>Cong, Hui</creatorcontrib><creatorcontrib>Chen, Hongmei</creatorcontrib><collection>Springer Nature OA Free Journals</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>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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>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>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pan, Yafang</au><au>Zhang, Yu</au><au>Liu, Wenwen</au><au>Huang, Yan</au><au>Shen, Xianjuan</au><au>Jing, Rongrong</au><au>Pu, Jiang</au><au>Wang, Xudong</au><au>Ju, Shaoqing</au><au>Cong, Hui</au><au>Chen, Hongmei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LncRNA H19 overexpression induces bortezomib resistance in multiple myeloma by targeting MCL-1 via miR-29b-3p</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2019-02-06</date><risdate>2019</risdate><volume>10</volume><issue>2</issue><spage>106</spage><pages>106-</pages><artnum>106</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Radiotherapy, chemotherapy, autologous/allogeneic stem cell transplantation, and targeted drug therapy are currently available therapeutic options for multiple myeloma (MM), but the clinical outcome remains unsatisfactory owing to frequent occurrence of drug resistance. Anti apoptosis is one of the main mechanisms to mediate drug resistance. Studies have shown that MCL-1 plays a key role in the growth of cancer cells “escaping” drug attacks, but the underlying mechanism remains unclear. Our previous study demonstrated that lncRNA H19 was highly expressed in the serum of MM patients. Bioinformatics predicts that miR-29b-3p is the downstream target gene, and MCL-1 is the downstream target protein of miR-29b-3p. Therefore, we speculated that MCL-1 may be involved in the occurrence of drug resistance through epigenetics. On the basis of these previous findings, the present study was intended to explore the biological function of H19, interactions between the downstream target genes, and the effect of H19 on BTZ resistance of myeloma cells. In addition, in vivo experiments we have also confirmed that H19 promoted tumor growth and may develop resistance to bortezomib partly. It was found that H19 reduced cell sensitivity to the chemotherapeutic drug BTZ by working as a miRNA sponge to inhibit the expression of miR-29b-3p, enhance MCL-1 transcriptional translation and inhibit apoptosis. These findings may help gain insights into the molecular mechanism of acquired BTZ resistance and develop new drug targets for the clinical treatment of MM.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30728351</pmid><doi>10.1038/s41419-018-1219-0</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 13/2 13/31 14/32 38/77 631/67 692/53 Antibodies Apoptosis Autografts Biochemistry Bioinformatics Biomedical and Life Sciences Bortezomib Cancer Cell Biology Cell Culture Chemotherapy Drug resistance Drug therapy Epigenetics Immunology Inhibitor drugs Life Sciences Mcl-1 protein miRNA Multiple myeloma Radiation therapy Stem cell transplantation Targeted cancer therapy Transcription |
| title | LncRNA H19 overexpression induces bortezomib resistance in multiple myeloma by targeting MCL-1 via miR-29b-3p |
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