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dc.creatorSaeinasab, M. (Morvarid)-
dc.creatorBahrami, A.R. (Ahmad Reza)-
dc.creatorGonzalez-Rojas, S.J. (Sandra Jovanna)-
dc.creatorMarchese, F.P. (Francesco P.)-
dc.creatorMartínez, D. (Dannys)-
dc.creatorMowla, S.J. (Seyed Javad)-
dc.creatorMatin, M.M. (Maryam M.)-
dc.creatorHuarte, M. (Maite)-
dc.date.accessioned2021-09-20T09:23:16Z-
dc.date.available2021-09-20T09:23:16Z-
dc.date.issued2019-
dc.identifier.citationSaeinasab, M. (Morvarid); Bahrami, A.R. (Ahmad Reza); Gonzalez-Rojas, S.J. (Sandra Jovanna); et al. "SNHG15 is a bifunctional MYC-regulated noncoding locus encoding a lncRNA that promotes cell proliferation, invasion and drug resistance in colorectal cancer by interacting with AIF". Journal of Experimental & Clinical Cancer Research. 38 (172), 2019, 1 - 16es
dc.identifier.issn1756-9966-
dc.identifier.otherPMID: 31014355-
dc.identifier.urihttps://hdl.handle.net/10171/62023-
dc.description.abstractBackground: Thousands of long noncoding RNAs (lncRNAs) are aberrantly expressed in various types of cancers, however our understanding of their role in the disease is still very limited. Methods: We applied RNAseq analysis from patient-derived data with validation in independent cohort of patients. We followed these studies with gene regulation analysis as well as experimental dissection of the role of the identified lncRNA by multiple in vitro and in vivo methods. Results: We analyzed RNA-seq data from tumors of 456 CRC patients compared to normal samples, and identified SNHG15 as a potentially oncogenic lncRNA that encodes a snoRNA in one of its introns. The processed SNHG15 is overexpressed in CRC tumors and its expression is highly correlated with poor survival of patients. Interestingly, SNHG15 is more highly expressed in tumors with high levels of MYC expression, while MYC protein binds to two E-box motifs on SNHG15 sequence, indicating that SNHG15 transcription is directly regulated by the oncogene MYC. The depletion of SNHG15 by siRNA or CRISPR-Cas9 inhibits cell proliferation and invasion, decreases colony formation as well as the tumorigenic capacity of CRC cells, whereas its overexpression leads to opposite effects. Gene expression analysis performed upon SNHG15 inhibition showed changes in multiple relevant genes implicated in cancer progression, including MYC, NRAS, BAG3 or ERBB3. Several of these genes are functionally related to AIF, a protein that we found to specifically interact with SNHG15, suggesting that the SNHG15 acts, at least in part, by regulating the activity of AIF. Interestingly, ROS levels, which are directly regulated by AIF, show a significant reduction in SNHG15-depleted cells. Moreover, knockdown of SNHG15 increases the sensitiveness of the cells to 5-FU, while its overexpression renders them more resistant to the chemotherapeutic drug. Conclusion: Altogether, these results describe an important role of SNHG15 in promoting colon cancer and mediating drug resistance, suggesting its potential as prognostic marker and target for RNA-based therapies.es_ES
dc.description.sponsorshipThis work has been supported by FEDER/Ministerio de Ciencia, Innovación y Universidades - Agencia Estatal de Investigación/ BFU2017–82773-P. This study was part of a PhD dissertation and was supported by Ferdowsi University of Mashhad (No. 41615).es_ES
dc.language.isoenges_ES
dc.publisherSpringer Science and Business Media LLCes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectMaterias Investigacion::Ciencias de la Salud::Oncologíaes_ES
dc.subjectAIFes_ES
dc.subjectColorectal canceres_ES
dc.subjectDrug resistancees_ES
dc.subjectSNHG15es_ES
dc.subjectSurvivales_ES
dc.subjectlncRNAes_ES
dc.titleSNHG15 is a bifunctional MYC-regulated noncoding locus encoding a lncRNA that promotes cell proliferation, invasion and drug resistance in colorectal cancer by interacting with AIFes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.description.noteThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). In the original publication of this article, the Funding section needs to be revised, and the corrected Funding section appears below. We apologize for any confusion this may have caused.es_ES
dc.identifier.doi10.1186/s13046-019-1169-0-
dadun.citation.endingPage16es_ES
dadun.citation.number172es_ES
dadun.citation.publicationNameJournal of Experimental & Clinical Cancer Researches_ES
dadun.citation.startingPage1es_ES
dadun.citation.volume38es_ES

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