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Expression profile of miR-17/92 cluster is predictive of treatment response in rectal cancer
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SYSNO ASEP 0496000 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Expression profile of miR-17/92 cluster is predictive of treatment response in rectal cancer Author(s) Král, Jan (UEM-P)
Korenková, Vlasta (BTO-N) RID
Novosadová, Vendula (UMG-J)
Langerová, Lucie (BTO-N) RID
Schneiderová, M. (CZ)
Liška, V. (CZ)
Levý, M. (CZ)
Veškrnová, V. (CZ)
Špičák, J. (CZ)
Opattová, Alena (UEM-P)
Jirásková, Kateřina (UEM-P)
Vymetálková, Veronika (UEM-P) RID
Vodička, Pavel (UEM-P) RID
Slyšková, Jana (UEM-P) RIDSource Title Carcinogenesis. - : Oxford University Press - ISSN 0143-3334
Roč. 39, č. 11 (2018), s. 1359-1367Number of pages 9 s. Language eng - English Country GB - United Kingdom Keywords colorectal-cancer ; microrna expression ; colon ; chemoradiotherapy Subject RIV EB - Genetics ; Molecular Biology OECD category Gastroenterology and hepatology Subject RIV - cooperation Institute of Biotechnology - Genetics ; Molecular Biology
Institute of Molecular GeneticsR&D Projects GA15-08239S GA ČR - Czech Science Foundation (CSF) NV15-26535A GA MZd - Ministry of Health (MZ) NV17-30920A GA MZd - Ministry of Health (MZ) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UEM-P - RVO:68378041 ; BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 UT WOS 000456033800006 EID SCOPUS 85058609966 DOI 10.1093/carcin/bgy100 Annotation MicroRNA (miRNA) profiling represents a promising source of cancer-related biomarkers. miRNA signatures are specific for each cancer type and subgroups of patients with diverse treatment sensitivity. Yet this miRNA potential has not been satisfactorily explored in rectal cancer (RC). The aim of the study was to identify the specific miRNA signature with clinical and therapeutic relevance for RC. Expressions of 2555 miRNA were examined in 20 pairs of rectal tumors and matched non-malignant tissues by 3D-Gene Toray microarray. Candidate miRNAs were validated in an independent cohort of 100 paired rectal tissues and in whole plasma and exosomes of 100 RC patients. To study the association of miRNA profile with therapeutic outcomes, plasma samples were taken repeatedly over a time period of 1 year reflecting thus patients' treatment responses. Finally, the most prominent miRNAs were investigated in vitro for their involvement in cell growth. We identified RC-specific miRNA signature that distinguishes responders from non-responders to adjuvant chemotherapy. A predominant part of identified miRNAs was represented by the members of miR-17/92 cluster. Upregulation of miRNA-17, -18a, -18b, -19a, -19b, -20a, -20b and -106a in tumor was associated with higher risk of tumor relapse and their overexpression in RC cell lines stimulated cellular proliferation. Examination of these miRNAs in plasma exosomes showed that their levels differed between RC patients and healthy controls and correlated with patient's treatment response. miRNAs from miR-17/92 cluster represent a non-invasive biomarker to predict posttreatment prognosis in RC patients. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2019
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