Cold-inducible RNA binding protein promotes breast cancer cell malignancy by regulating Cystatin C levels

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• dc.contributor.author Indacochea Cusirramos, Alberto
• dc.contributor.author Guerrero Jijon, Santiago Xavier
• dc.contributor.author Ureña, Macarena
• dc.contributor.author Araujo, Ferrán
• dc.contributor.author Coll, Olga
• dc.contributor.author Lleonart, Matilde E.
• dc.contributor.author Gebauer, Fátima
• dc.date.accessioned 2021-03-24T09:12:08Z
• dc.date.available 2021-03-24T09:12:08Z
• dc.date.issued 2021
• dc.description.abstract Cold-inducible RNA binding protein (CIRBP) is a stress-responsive protein that promotes cancer development and inflammation. Critical to most CIRBP functions is its capacity to bind and posttranscriptionally modulate mRNA. However, a transcriptome-wide analysis of CIRBP mRNA targets in cancer has not yet been performed. Here, we use an ex vivo breast cancer model to identify CIRBP targets and mechanisms. We find that CIRBP transcript levels correlate with breast cancer subtype and are an indicator of luminal A/B prognosis. Accordingly, overexpression of CIRBP in nontumoral MCF-10A cells promotes cell growth and clonogenicity, while depletion of CIRBP from luminal A MCF-7 cells has opposite effects. We use RNA immunoprecipitation followed by high-throughput sequencing (RIP-seq) to identify a set of 204 high confident CIRBP targets in MCF-7 cells. About 10% of these showed complementary changes after CIRBP manipulation in MCF-10A and MCF-7 cells, and were highly interconnected with known breast cancer genes. To test the potential of CIRBP-mediated regulation of these targets in breast cancer development, we focused on Cystatin C (CST3), one of the most highly interconnected genes, encoding a protein that displays tumor suppressive capacities. CST3 depletion restored the effects of CIRBP depletion in MCF-7 cells, indicating that CIRBP functions, at least in part, by down-regulating CST3 levels. Our data provide a resource of CIRBP targets in breast cancer, and identify CST3 as a novel downstream mediator of CIRBP function.
• dc.description.sponsorship Funding: A.I. was supported by a CRG PhD4MD fellowship. F.G. was supported by grants from the Spanish Ministry of Science and Innovation (MICINN, PGC2018-099697-B-I00), “la Caixa” Foundation (ID 100010434) under the agreement LCF/PR/HR17/52150016, the Catalan Agency for Research and Universities (2017SGR534), and the Centre of Excellence Severo Ochoa. M.E.LL. was supported by grants from the Instituto de Salud Carlos III:PI15/01262 and CP03/00101 cofinanced by the European Regional Fund (ERDF) and AECC Funding ref. GC16173720CARR
• dc.format.mimetype application/pdf*
• dc.identifier.citation Indaochea A, Guerrero S, Ureña M, Araujo F, Coll O, Lleonart MA et al. Cold-inducible RNA binding protein promotes breast cancer cell malignancy by regulating Cystatin C levels. RNA. 2021 Feb;27(2):190-201. DOI: 10.1261/rna.076422.120
• dc.identifier.doi http://dx.doi.org/ 10.1261/rna.076422.120
• dc.identifier.issn 1355-8382
• dc.identifier.uri http://hdl.handle.net/10230/46921
• dc.language.iso eng
• dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)
• dc.relation.ispartof RNA. 2021 Feb;27(2):190-201
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-099697-B-I00
• dc.rights © 2021 Indacochea et al. This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Mama -- Càncer
• dc.subject.other Proteïnes
• dc.subject.other RNA
• dc.title Cold-inducible RNA binding protein promotes breast cancer cell malignancy by regulating Cystatin C levels
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion