miRNAs in multiple myeloma - a survival relevant complex regulator of gene expression
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| Název: | miRNAs in multiple myeloma - a survival relevant complex regulator of gene expression |
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| Autoři: | Seckinger, Anja, Meißner, Tobias, Moreaux, Jerome, Benes, Vladimir, Hillengass, Jens, Castoldi, Mirco, Zimmermann, Jürgen, Ho, Anthony D, Jauch, Anna, Goldschmidt, Hartmut, Klein, Bernard, Hose, Dirk |
| Přispěvatelé: | FORMER_Hematology, Basic (bio-) Medical Sciences |
| Zdroj: | Oncotarget. 6:39165-39183 |
| Informace o vydavateli: | Impact Journals, LLC, 2015. |
| Rok vydání: | 2015 |
| Témata: | 0301 basic medicine, 0303 health sciences, Gene Expression Profiling, Plasma Cells, Multiple Myeloma/genetics, Plasma Cells/physiology, MicroRNAs/biosynthesis, Prognosis, Survival Analysis, 3. Good health, Cohort Studies, Gene Expression Regulation, Neoplastic, Cell Proliferation/genetics, MicroRNAs, 03 medical and health sciences, Cohort studies, Humans, Multiple Myeloma, Cell Proliferation |
| Popis: | microRNAs regulate gene-expression in biological and pathophysiological processes, including multiple myeloma. Here we address i) What are the number and magnitude of changes in miRNA-expression between normal plasma cells and myeloma- or MGUS-samples, and the latter two? ii) What is the biological relevance and how does miRNA-expression impact on gene-expression? iii) Is there a prognostic significance, and what is its background?Ninety-two purified myeloma-, MGUS-, normal plasma cell- and myeloma cell line-samples were investigated using miChip-arrays interrogating 559 human miRNAs. Impact on gene-expression was assessed by Affymetrix DNA-microarrays in two cohorts of myeloma patients (n = 677); chromosomal aberrations were assessed by iFISH, survival for 592 patients undergoing up-front high-dose chemotherapy.Compared to normal plasma cells, 67/559 miRNAs (12%) with fold changes of 4.6 to -3.1 are differentially expressed in myeloma-, 20 (3.6%) in MGUS-samples, and three (0.5%) between MGUS and myeloma. Expression of miRNAs is associated with proliferation, chromosomal aberrations, tumor mass, and gene expression-based risk-scores. This holds true for target-gene signatures of regulated mRNAs. miRNA-expression confers prognostic significance for event-free and overall survival, as do respective target-gene signatures.The myeloma-miRNome confers a pattern of small changes of individual miRNAs impacting on gene-expression, biological functions, and survival. |
| Druh dokumentu: | Article |
| Jazyk: | English |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.5381 |
| Přístupová URL adresa: | http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=5381&path%5B%5D=15052 https://pubmed.ncbi.nlm.nih.gov/26472281 https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=5381&path%5B%5D=15052 https://www.oncotarget.com/fulltext/5381 https://www.ncbi.nlm.nih.gov/pubmed/26472281 https://hal.archives-ouvertes.fr/hal-01237028 https://europepmc.org/articles/PMC4770764 https://pubmed.ncbi.nlm.nih.gov/26472281/ https://biblio.vub.ac.be/vubir/mirnas-in-multiple-myelomaa-survival-relevant-complex-regulator-of-gene-expression(f4cbe422-8353-4e97-9380-38e200f5ee49).html https://hdl.handle.net/20.500.14017/f4cbe422-8353-4e97-9380-38e200f5ee49 https://doi.org/10.18632/oncotarget.5381 |
| Rights: | CC BY |
| Přístupové číslo: | edsair.doi.dedup.....33cfef400d0d6c10e970fdb848c7d376 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | microRNAs regulate gene-expression in biological and pathophysiological processes, including multiple myeloma. Here we address i) What are the number and magnitude of changes in miRNA-expression between normal plasma cells and myeloma- or MGUS-samples, and the latter two? ii) What is the biological relevance and how does miRNA-expression impact on gene-expression? iii) Is there a prognostic significance, and what is its background?Ninety-two purified myeloma-, MGUS-, normal plasma cell- and myeloma cell line-samples were investigated using miChip-arrays interrogating 559 human miRNAs. Impact on gene-expression was assessed by Affymetrix DNA-microarrays in two cohorts of myeloma patients (n = 677); chromosomal aberrations were assessed by iFISH, survival for 592 patients undergoing up-front high-dose chemotherapy.Compared to normal plasma cells, 67/559 miRNAs (12%) with fold changes of 4.6 to -3.1 are differentially expressed in myeloma-, 20 (3.6%) in MGUS-samples, and three (0.5%) between MGUS and myeloma. Expression of miRNAs is associated with proliferation, chromosomal aberrations, tumor mass, and gene expression-based risk-scores. This holds true for target-gene signatures of regulated mRNAs. miRNA-expression confers prognostic significance for event-free and overall survival, as do respective target-gene signatures.The myeloma-miRNome confers a pattern of small changes of individual miRNAs impacting on gene-expression, biological functions, and survival. |
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| ISSN: | 19492553 |
| DOI: | 10.18632/oncotarget.5381 |