Pseudogene KRT17P3 drives cisplatin resistance of human NSCLC cells by modulating miR‐497‐5p/mTOR
Chemoresistance is a major obstacle in non–small cell lung cancer (NSCLC) treatment. The pseudogene keratin 17 pseudogene 3 (KRT17P3) has been previously shown to be upregulated in lung cancer tissues of patients with cisplatin resistance. In the present study, RT‐qPCR was performed to evaluate KRT1...
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| description | Chemoresistance is a major obstacle in non–small cell lung cancer (NSCLC) treatment. The pseudogene keratin 17 pseudogene 3 (KRT17P3) has been previously shown to be upregulated in lung cancer tissues of patients with cisplatin resistance. In the present study, RT‐qPCR was performed to evaluate KRT17P3 levels in plasma samples collected from 30 cisplatin‐resistant and 32 cisplatin‐sensitive patients. We found that the plasma level of KRT17P3 is upregulated in cisplatin‐resistant patients, and the increased expression of plasma KRT17P3 is associated with poor chemotherapy response. Functional studies demonstrated that KRT17P3 overexpression in cultured NSCLC cells increases cell viability and decreases apoptosis upon cisplatin treatment in vitro and in vivo, while KRT17P3 knockdown has the opposite effect. Mechanistically, bioinformatics analysis, RNA immunoprecipitation, and dual luciferase reporter assay indicated that KRT17P3 acts as a molecular sponge for miR‐497‐5p and relieves the binding of miR‐497‐5p to its target gene mTOR. Rescue experiments validated the functional interaction between KRT17P3, miR‐497‐5p, and mTOR. Taken together, our findings indicate that KRT17P3/miR‐497‐5p/mTOR regulates the chemosensitivity of NSCLC, suggesting a potential therapeutic target for cisplatin‐resistant NSCLC patients. KRT17P3 may be a potential peripheral blood marker of NSCLC patients resistant to cisplatin.
In the present study, we found the plasma level of KRT17P3 is upregulated in cisplatin‐resistant patients, and the increased expression of plasma KRT17P3 is associated with poor chemotherapy response. Functional studies demonstrated that KRT17P3 overexpression in cultured NSCLC cells increases cell viability and decreases apoptosis upon cisplatin treatment in vitro and in vivo, while KRT17P3 knockdown has the opposite effect. Mechanistically, KRT17P3 acts as a molecular sponge for miR‐497‐5p and relieves the binding of miR‐497‐5p to its target gene mTOR. |
| doi_str_mv | 10.1111/cas.14733 |
| format | Article |
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In the present study, we found the plasma level of KRT17P3 is upregulated in cisplatin‐resistant patients, and the increased expression of plasma KRT17P3 is associated with poor chemotherapy response. Functional studies demonstrated that KRT17P3 overexpression in cultured NSCLC cells increases cell viability and decreases apoptosis upon cisplatin treatment in vitro and in vivo, while KRT17P3 knockdown has the opposite effect. Mechanistically, KRT17P3 acts as a molecular sponge for miR‐497‐5p and relieves the binding of miR‐497‐5p to its target gene mTOR.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.14733</identifier><identifier>PMID: 33179318</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Aged ; Animals ; Apoptosis ; Bioinformatics ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Cell Line, Tumor ; Cell viability ; Cell, Molecular, and Stem Cell Biology ; Chemoresistance ; Chemotherapy ; Chromosome 5 ; Cisplatin ; Cisplatin - therapeutic use ; Drug resistance ; Drug Resistance, Neoplasm - genetics ; Female ; Gastric cancer ; Gene expression ; Gene Expression Regulation, Neoplastic - genetics ; Heterografts ; Humans ; Immunoprecipitation ; Keratin ; Keratin-17 - genetics ; KRT17P3 ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Male ; Metastasis ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; miR‐497‐5p ; mTOR ; Non-small cell lung carcinoma ; non–small‐cell lung cancer ; Original ; Peripheral blood ; Plasma ; Plasmids ; Polymerase chain reaction ; Pseudogenes - genetics ; Ribonucleic acid ; RNA ; Small cell lung carcinoma ; Software ; TOR protein ; TOR Serine-Threonine Kinases - genetics ; TOR Serine-Threonine Kinases - metabolism</subject><ispartof>Cancer science, 2021-01, Vol.112 (1), p.275-286</ispartof><rights>2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by-nc-nd/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-c4673-3d3462256c530156763bc255e5921f685f1e8cc5914b921538c0f6db136b4db53</citedby><cites>FETCH-LOGICAL-c4673-3d3462256c530156763bc255e5921f685f1e8cc5914b921538c0f6db136b4db53</cites><orcidid>0000-0003-4979-4131 ; 0000-0002-3084-5624</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/PMC7780050/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780050/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33179318$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hou, Zhibo</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Xia, Ning</creatorcontrib><creatorcontrib>Lv, Tangfeng</creatorcontrib><creatorcontrib>Yuan, Xiaoqin</creatorcontrib><creatorcontrib>Song, Yong</creatorcontrib><title>Pseudogene KRT17P3 drives cisplatin resistance of human NSCLC cells by modulating miR‐497‐5p/mTOR</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Chemoresistance is a major obstacle in non–small cell lung cancer (NSCLC) treatment. The pseudogene keratin 17 pseudogene 3 (KRT17P3) has been previously shown to be upregulated in lung cancer tissues of patients with cisplatin resistance. In the present study, RT‐qPCR was performed to evaluate KRT17P3 levels in plasma samples collected from 30 cisplatin‐resistant and 32 cisplatin‐sensitive patients. We found that the plasma level of KRT17P3 is upregulated in cisplatin‐resistant patients, and the increased expression of plasma KRT17P3 is associated with poor chemotherapy response. Functional studies demonstrated that KRT17P3 overexpression in cultured NSCLC cells increases cell viability and decreases apoptosis upon cisplatin treatment in vitro and in vivo, while KRT17P3 knockdown has the opposite effect. Mechanistically, bioinformatics analysis, RNA immunoprecipitation, and dual luciferase reporter assay indicated that KRT17P3 acts as a molecular sponge for miR‐497‐5p and relieves the binding of miR‐497‐5p to its target gene mTOR. Rescue experiments validated the functional interaction between KRT17P3, miR‐497‐5p, and mTOR. Taken together, our findings indicate that KRT17P3/miR‐497‐5p/mTOR regulates the chemosensitivity of NSCLC, suggesting a potential therapeutic target for cisplatin‐resistant NSCLC patients. KRT17P3 may be a potential peripheral blood marker of NSCLC patients resistant to cisplatin.
In the present study, we found the plasma level of KRT17P3 is upregulated in cisplatin‐resistant patients, and the increased expression of plasma KRT17P3 is associated with poor chemotherapy response. Functional studies demonstrated that KRT17P3 overexpression in cultured NSCLC cells increases cell viability and decreases apoptosis upon cisplatin treatment in vitro and in vivo, while KRT17P3 knockdown has the opposite effect. Mechanistically, KRT17P3 acts as a molecular sponge for miR‐497‐5p and relieves the binding of miR‐497‐5p to its target gene mTOR.</description><subject>Aged</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Bioinformatics</subject><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell viability</subject><subject>Cell, Molecular, and Stem Cell Biology</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Chromosome 5</subject><subject>Cisplatin</subject><subject>Cisplatin - therapeutic use</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Keratin</subject><subject>Keratin-17 - genetics</subject><subject>KRT17P3</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Male</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>miR‐497‐5p</subject><subject>mTOR</subject><subject>Non-small cell lung carcinoma</subject><subject>non–small‐cell lung cancer</subject><subject>Original</subject><subject>Peripheral blood</subject><subject>Plasma</subject><subject>Plasmids</subject><subject>Polymerase chain reaction</subject><subject>Pseudogenes - genetics</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Small cell lung carcinoma</subject><subject>Software</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - genetics</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kctO3DAUhq0KVCjtghdAlti0izB2ji_JBglFvYkRoGG6thzHGYySeGpPqGbXR-gz9knqmaGoINUL--j406dz9CN0TMkZTWdidDyjTAK8QocUWJlJQsTetpZZSSA_QG9ivCcEBCvZa3QAQGUJtDhE9ibasfELO1h8OZtTeQO4Ce7BRmxcXHZ65QYcbHRxpQdjsW_x3djrAV_dVtMKG9t1Eddr3Ptm3MIL3LvZ75-_WCnTzZeTfn49e4v2W91F--7xPULfPn2cV1-y6fXnr9XFNDNMSMigASbynAvDgVAupIDa5JxbXua0FQVvqS2M4SVldepwKAxpRVNTEDVrag5H6HznXY51bxtjh1XQnVoG1-uwVl479fxncHdq4R-UlAUhnCTB-0dB8N9HG1eqd3GzpB6sH6PKmSCkyPMCEnr6Ar33YxjSeomSTIpCio3ww44ywccYbPs0DCVqE55K4alteIk9-Xf6J_JvWgmY7IAfrrPr_5tUdXG7U_4BE9Wi9g</recordid><startdate>202101</startdate><enddate>202101</enddate><creator>Hou, Zhibo</creator><creator>Wang, Yi</creator><creator>Xia, Ning</creator><creator>Lv, Tangfeng</creator><creator>Yuan, Xiaoqin</creator><creator>Song, Yong</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><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>8FE</scope><scope>8FH</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>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4979-4131</orcidid><orcidid>https://orcid.org/0000-0002-3084-5624</orcidid></search><sort><creationdate>202101</creationdate><title>Pseudogene KRT17P3 drives cisplatin resistance of human NSCLC cells by modulating miR‐497‐5p/mTOR</title><author>Hou, Zhibo ; Wang, Yi ; Xia, Ning ; Lv, Tangfeng ; Yuan, Xiaoqin ; Song, Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4673-3d3462256c530156763bc255e5921f685f1e8cc5914b921538c0f6db136b4db53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Bioinformatics</topic><topic>Cancer therapies</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell viability</topic><topic>Cell, Molecular, and Stem Cell Biology</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>Chromosome 5</topic><topic>Cisplatin</topic><topic>Cisplatin - therapeutic use</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Keratin</topic><topic>Keratin-17 - genetics</topic><topic>KRT17P3</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Male</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>miR‐497‐5p</topic><topic>mTOR</topic><topic>Non-small cell lung carcinoma</topic><topic>non–small‐cell lung cancer</topic><topic>Original</topic><topic>Peripheral blood</topic><topic>Plasma</topic><topic>Plasmids</topic><topic>Polymerase chain reaction</topic><topic>Pseudogenes - genetics</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Small cell lung carcinoma</topic><topic>Software</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - genetics</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hou, Zhibo</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Xia, Ning</creatorcontrib><creatorcontrib>Lv, Tangfeng</creatorcontrib><creatorcontrib>Yuan, Xiaoqin</creatorcontrib><creatorcontrib>Song, Yong</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hou, Zhibo</au><au>Wang, Yi</au><au>Xia, Ning</au><au>Lv, Tangfeng</au><au>Yuan, Xiaoqin</au><au>Song, Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pseudogene KRT17P3 drives cisplatin resistance of human NSCLC cells by modulating miR‐497‐5p/mTOR</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2021-01</date><risdate>2021</risdate><volume>112</volume><issue>1</issue><spage>275</spage><epage>286</epage><pages>275-286</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Chemoresistance is a major obstacle in non–small cell lung cancer (NSCLC) treatment. The pseudogene keratin 17 pseudogene 3 (KRT17P3) has been previously shown to be upregulated in lung cancer tissues of patients with cisplatin resistance. In the present study, RT‐qPCR was performed to evaluate KRT17P3 levels in plasma samples collected from 30 cisplatin‐resistant and 32 cisplatin‐sensitive patients. We found that the plasma level of KRT17P3 is upregulated in cisplatin‐resistant patients, and the increased expression of plasma KRT17P3 is associated with poor chemotherapy response. Functional studies demonstrated that KRT17P3 overexpression in cultured NSCLC cells increases cell viability and decreases apoptosis upon cisplatin treatment in vitro and in vivo, while KRT17P3 knockdown has the opposite effect. Mechanistically, bioinformatics analysis, RNA immunoprecipitation, and dual luciferase reporter assay indicated that KRT17P3 acts as a molecular sponge for miR‐497‐5p and relieves the binding of miR‐497‐5p to its target gene mTOR. Rescue experiments validated the functional interaction between KRT17P3, miR‐497‐5p, and mTOR. Taken together, our findings indicate that KRT17P3/miR‐497‐5p/mTOR regulates the chemosensitivity of NSCLC, suggesting a potential therapeutic target for cisplatin‐resistant NSCLC patients. KRT17P3 may be a potential peripheral blood marker of NSCLC patients resistant to cisplatin.
In the present study, we found the plasma level of KRT17P3 is upregulated in cisplatin‐resistant patients, and the increased expression of plasma KRT17P3 is associated with poor chemotherapy response. Functional studies demonstrated that KRT17P3 overexpression in cultured NSCLC cells increases cell viability and decreases apoptosis upon cisplatin treatment in vitro and in vivo, while KRT17P3 knockdown has the opposite effect. Mechanistically, KRT17P3 acts as a molecular sponge for miR‐497‐5p and relieves the binding of miR‐497‐5p to its target gene mTOR.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>33179318</pmid><doi>10.1111/cas.14733</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4979-4131</orcidid><orcidid>https://orcid.org/0000-0002-3084-5624</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Animals Apoptosis Bioinformatics Cancer therapies Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Cell Line, Tumor Cell viability Cell, Molecular, and Stem Cell Biology Chemoresistance Chemotherapy Chromosome 5 Cisplatin Cisplatin - therapeutic use Drug resistance Drug Resistance, Neoplasm - genetics Female Gastric cancer Gene expression Gene Expression Regulation, Neoplastic - genetics Heterografts Humans Immunoprecipitation Keratin Keratin-17 - genetics KRT17P3 Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - metabolism Male Metastasis Mice Mice, Inbred BALB C Mice, Nude MicroRNAs - genetics MicroRNAs - metabolism Middle Aged miR‐497‐5p mTOR Non-small cell lung carcinoma non–small‐cell lung cancer Original Peripheral blood Plasma Plasmids Polymerase chain reaction Pseudogenes - genetics Ribonucleic acid RNA Small cell lung carcinoma Software TOR protein TOR Serine-Threonine Kinases - genetics TOR Serine-Threonine Kinases - metabolism |
| title | Pseudogene KRT17P3 drives cisplatin resistance of human NSCLC cells by modulating miR‐497‐5p/mTOR |
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