Upregulation of the novel lncRNA U731166 is associated with migration, invasion and vemurafenib resistance in melanoma
Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and cand...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2022-02, Vol.26 (3), p.671-683 |
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| creator | Siena, Ádamo Davi Diógenes Barros, Isabela Ichihara de Storti, Camila Baldin de Biagi Júnior, Carlos Alberto Oliveira da Costa Carvalho, Larissa Anastacio Maria‐Engler, Silvya Stuchi Sousa, Josane de Freitas Silva, Wilson Araújo |
| description | Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis‐related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naïve and vemurafenib‐resistant cell lines and data from a patient before and after resistance, we found that vemurafenib‐resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance. |
| doi_str_mv | 10.1111/jcmm.16987 |
| format | Article |
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Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis‐related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naïve and vemurafenib‐resistant cell lines and data from a patient before and after resistance, we found that vemurafenib‐resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.16987</identifier><identifier>PMID: 35040264</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Biomarkers ; Cell Line, Tumor ; Cell Proliferation ; Drug resistance ; Drug Resistance, Neoplasm - genetics ; ENSG00000230454 ; Gene expression ; Humans ; invasion ; Invasiveness ; lncRNAs ; Medical research ; Melanocytes ; Melanoma ; Melanoma - drug therapy ; Melanoma - genetics ; Melanoma - metabolism ; Metastases ; migration ; Mutation ; Neoplasm Invasiveness - genetics ; Non-coding RNA ; Original ; Patients ; Phenotypes ; resistance ; RNA processing ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; Skin cancer ; U73166 ; Up-Regulation - genetics ; vemurafenib ; Vemurafenib - pharmacology</subject><ispartof>Journal of cellular and molecular medicine, 2022-02, Vol.26 (3), p.671-683</ispartof><rights>2022 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2022. 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-c4487-f71b7693a98303e4b3a26b3e088ea17934f2b8e3ca332aa55c2fecf6da267bf43</citedby><cites>FETCH-LOGICAL-c4487-f71b7693a98303e4b3a26b3e088ea17934f2b8e3ca332aa55c2fecf6da267bf43</cites><orcidid>0000-0001-5720-5910 ; 0000-0002-8468-7609 ; 0000-0003-0700-3135 ; 0000-0001-9364-2886 ; 0000-0003-2462-7767 ; 0000-0003-3556-9160 ; 0000-0003-4771-6041 ; 0000-0001-7932-9818</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/PMC8817119/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8817119/$$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/35040264$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Siena, Ádamo Davi Diógenes</creatorcontrib><creatorcontrib>Barros, Isabela Ichihara de</creatorcontrib><creatorcontrib>Storti, Camila Baldin</creatorcontrib><creatorcontrib>de Biagi Júnior, Carlos Alberto Oliveira</creatorcontrib><creatorcontrib>da Costa Carvalho, Larissa Anastacio</creatorcontrib><creatorcontrib>Maria‐Engler, Silvya Stuchi</creatorcontrib><creatorcontrib>Sousa, Josane de Freitas</creatorcontrib><creatorcontrib>Silva, Wilson Araújo</creatorcontrib><title>Upregulation of the novel lncRNA U731166 is associated with migration, invasion and vemurafenib resistance in melanoma</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis‐related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naïve and vemurafenib‐resistant cell lines and data from a patient before and after resistance, we found that vemurafenib‐resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance.</description><subject>Biomarkers</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>ENSG00000230454</subject><subject>Gene expression</subject><subject>Humans</subject><subject>invasion</subject><subject>Invasiveness</subject><subject>lncRNAs</subject><subject>Medical research</subject><subject>Melanocytes</subject><subject>Melanoma</subject><subject>Melanoma - drug therapy</subject><subject>Melanoma - genetics</subject><subject>Melanoma - metabolism</subject><subject>Metastases</subject><subject>migration</subject><subject>Mutation</subject><subject>Neoplasm Invasiveness - genetics</subject><subject>Non-coding RNA</subject><subject>Original</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>resistance</subject><subject>RNA processing</subject><subject>RNA, Long Noncoding - genetics</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>Skin cancer</subject><subject>U73166</subject><subject>Up-Regulation - genetics</subject><subject>vemurafenib</subject><subject>Vemurafenib - pharmacology</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kcFuEzEQhi0EoiVw4QGQJS4IkWKvvWvvBamKgFK1ICFytmad2cTRrh3s3a369jhNWkEP-GJL8_nTzPyEvObsjOfzcWv7_oxXtVZPyCkvdTGXtZBPj2-uhT4hL1LaMiYqLurn5ESUTLKikqdkWu4irscOBhc8DS0dNkh9mLCjnbc_v5_TpRKcVxV1iUJKwToYcEVv3LChvVvHu48fqPMTpL0C_IpO2I8RWvSuoRGTSwN4i5mhPXbgQw8vybMWuoSvjveMLL98_rW4mF_9-PptcX41t1JqNW8Vb1RVC6i1YAJlI6CoGoFMawSu8pRt0WgUFoQoAMrSFi3atlplTDWtFDPy6eDdjU2PK4t-iNCZXXQ9xFsTwJl_K95tzDpMRmuuOK-z4N1REMPvEdNgepcsdnkMDGMyRVVwllecFzsjbx-h2zBGn8fbU6UstVQsU-8PlI0hpYjtQzOcmX2cZh-nuYszw2_-bv8Bvc8vA_wA3LgOb_-jMpeL6-uD9A_2_6wF</recordid><startdate>202202</startdate><enddate>202202</enddate><creator>Siena, Ádamo Davi Diógenes</creator><creator>Barros, Isabela Ichihara de</creator><creator>Storti, Camila Baldin</creator><creator>de Biagi Júnior, Carlos Alberto Oliveira</creator><creator>da Costa Carvalho, Larissa Anastacio</creator><creator>Maria‐Engler, Silvya Stuchi</creator><creator>Sousa, Josane de Freitas</creator><creator>Silva, Wilson Araújo</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5720-5910</orcidid><orcidid>https://orcid.org/0000-0002-8468-7609</orcidid><orcidid>https://orcid.org/0000-0003-0700-3135</orcidid><orcidid>https://orcid.org/0000-0001-9364-2886</orcidid><orcidid>https://orcid.org/0000-0003-2462-7767</orcidid><orcidid>https://orcid.org/0000-0003-3556-9160</orcidid><orcidid>https://orcid.org/0000-0003-4771-6041</orcidid><orcidid>https://orcid.org/0000-0001-7932-9818</orcidid></search><sort><creationdate>202202</creationdate><title>Upregulation of the novel lncRNA U731166 is associated with migration, invasion and vemurafenib resistance in melanoma</title><author>Siena, Ádamo Davi Diógenes ; Barros, Isabela Ichihara de ; Storti, Camila Baldin ; de Biagi Júnior, Carlos Alberto Oliveira ; da Costa Carvalho, Larissa Anastacio ; Maria‐Engler, Silvya Stuchi ; Sousa, Josane de Freitas ; Silva, Wilson Araújo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4487-f71b7693a98303e4b3a26b3e088ea17934f2b8e3ca332aa55c2fecf6da267bf43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biomarkers</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>ENSG00000230454</topic><topic>Gene expression</topic><topic>Humans</topic><topic>invasion</topic><topic>Invasiveness</topic><topic>lncRNAs</topic><topic>Medical research</topic><topic>Melanocytes</topic><topic>Melanoma</topic><topic>Melanoma - drug therapy</topic><topic>Melanoma - genetics</topic><topic>Melanoma - metabolism</topic><topic>Metastases</topic><topic>migration</topic><topic>Mutation</topic><topic>Neoplasm Invasiveness - genetics</topic><topic>Non-coding RNA</topic><topic>Original</topic><topic>Patients</topic><topic>Phenotypes</topic><topic>resistance</topic><topic>RNA processing</topic><topic>RNA, Long Noncoding - genetics</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>Skin cancer</topic><topic>U73166</topic><topic>Up-Regulation - genetics</topic><topic>vemurafenib</topic><topic>Vemurafenib - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Siena, Ádamo Davi Diógenes</creatorcontrib><creatorcontrib>Barros, Isabela Ichihara de</creatorcontrib><creatorcontrib>Storti, Camila Baldin</creatorcontrib><creatorcontrib>de Biagi Júnior, Carlos Alberto Oliveira</creatorcontrib><creatorcontrib>da Costa Carvalho, Larissa Anastacio</creatorcontrib><creatorcontrib>Maria‐Engler, Silvya Stuchi</creatorcontrib><creatorcontrib>Sousa, Josane de Freitas</creatorcontrib><creatorcontrib>Silva, Wilson Araújo</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 Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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>Engineering Research Database</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>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Siena, Ádamo Davi Diógenes</au><au>Barros, Isabela Ichihara de</au><au>Storti, Camila Baldin</au><au>de Biagi Júnior, Carlos Alberto Oliveira</au><au>da Costa Carvalho, Larissa Anastacio</au><au>Maria‐Engler, Silvya Stuchi</au><au>Sousa, Josane de Freitas</au><au>Silva, Wilson Araújo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of the novel lncRNA U731166 is associated with migration, invasion and vemurafenib resistance in melanoma</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2022-02</date><risdate>2022</risdate><volume>26</volume><issue>3</issue><spage>671</spage><epage>683</epage><pages>671-683</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis‐related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naïve and vemurafenib‐resistant cell lines and data from a patient before and after resistance, we found that vemurafenib‐resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>35040264</pmid><doi>10.1111/jcmm.16987</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-5720-5910</orcidid><orcidid>https://orcid.org/0000-0002-8468-7609</orcidid><orcidid>https://orcid.org/0000-0003-0700-3135</orcidid><orcidid>https://orcid.org/0000-0001-9364-2886</orcidid><orcidid>https://orcid.org/0000-0003-2462-7767</orcidid><orcidid>https://orcid.org/0000-0003-3556-9160</orcidid><orcidid>https://orcid.org/0000-0003-4771-6041</orcidid><orcidid>https://orcid.org/0000-0001-7932-9818</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Biomarkers Cell Line, Tumor Cell Proliferation Drug resistance Drug Resistance, Neoplasm - genetics ENSG00000230454 Gene expression Humans invasion Invasiveness lncRNAs Medical research Melanocytes Melanoma Melanoma - drug therapy Melanoma - genetics Melanoma - metabolism Metastases migration Mutation Neoplasm Invasiveness - genetics Non-coding RNA Original Patients Phenotypes resistance RNA processing RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism Skin cancer U73166 Up-Regulation - genetics vemurafenib Vemurafenib - pharmacology |
| title | Upregulation of the novel lncRNA U731166 is associated with migration, invasion and vemurafenib resistance in melanoma |
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