MiR-15a and miR-16-1 cluster functions in human leukemia

George A. Calin; Amelia Cimmino; Muller Fabbri; Manuela Ferracin; Sylwia E. Wojcik; Masayoshi Shimizu; Cristian Taccioli; Nicola Zanesi; Ramiro Garzon; Rami I. Aqeilan; Hansjuerg Alder; Stefano Volinia; Laura Rassenti; Xiuping Liu; Chang Gong Liu; Thomas J. Kipps; Massimo Negrini; Carlo M. Croce

doi:10.1073/pnas.0800121105

MiR-15a and miR-16-1 cluster functions in human leukemia

George A. Calin, Amelia Cimmino, Muller Fabbri, Manuela Ferracin, Sylwia E. Wojcik, Masayoshi Shimizu, Cristian Taccioli, Nicola Zanesi, Ramiro Garzon, Rami I. Aqeilan, Hansjuerg Alder, Stefano Volinia, Laura Rassenti, Xiuping Liu, Chang Gong Liu, Thomas J. Kipps, Massimo Negrini, Carlo M. Croce

Research output: Contribution to journal › Article › peer-review

662 Scopus citations

Abstract

MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression that play roles in human diseases, including cancer. Each miRNA is predicted to regulate hundreds of transcripts, but only few have experimental validation. In chronic lymphocytic leukemia (CLL), the most common adult human leukemia, miR-15a and miR-16-1 are lost or down-regulated in the majority of cases. After our previous work indicating a tumor suppressor function of miR-15a/16-1 by targeting the BCL2 oncogene, here, we produced a high-throughput profiling of genes modulated by miR-15a/16-1 in a leukemic cell line model (MEG-01) and in primary CLL samples. By combining experimental and bioinformatics data, we identified a miR-15a/16-1-gene signature in leukemic cells. Among the components of the miR-15a/16-1 signature, we observed a statistically significant enrichment in AU-rich elements (AREs). By examining the Gene Ontology (GO) database, a significant enrichment in cancer genes (such as MCL1, BCL2, ETS1, or JUN) that directly or indirectly affect apoptosis and cell cycle was found.

Original language	American English
Pages (from-to)	5166-5171
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	105
Issue number	13
DOIs	https://doi.org/10.1073/pnas.0800121105
State	Published - 1 Apr 2008
Externally published	Yes

Keywords

Cancer
MicroRNA
Targets

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.0800121105

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Calin, G. A., Cimmino, A., Fabbri, M., Ferracin, M., Wojcik, S. E., Shimizu, M., Taccioli, C., Zanesi, N., Garzon, R., Aqeilan, R. I., Alder, H., Volinia, S., Rassenti, L., Liu, X., Liu, C. G., Kipps, T. J., Negrini, M., & Croce, C. M. (2008). MiR-15a and miR-16-1 cluster functions in human leukemia. Proceedings of the National Academy of Sciences of the United States of America, 105(13), 5166-5171. https://doi.org/10.1073/pnas.0800121105

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title = "MiR-15a and miR-16-1 cluster functions in human leukemia",

abstract = "MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression that play roles in human diseases, including cancer. Each miRNA is predicted to regulate hundreds of transcripts, but only few have experimental validation. In chronic lymphocytic leukemia (CLL), the most common adult human leukemia, miR-15a and miR-16-1 are lost or down-regulated in the majority of cases. After our previous work indicating a tumor suppressor function of miR-15a/16-1 by targeting the BCL2 oncogene, here, we produced a high-throughput profiling of genes modulated by miR-15a/16-1 in a leukemic cell line model (MEG-01) and in primary CLL samples. By combining experimental and bioinformatics data, we identified a miR-15a/16-1-gene signature in leukemic cells. Among the components of the miR-15a/16-1 signature, we observed a statistically significant enrichment in AU-rich elements (AREs). By examining the Gene Ontology (GO) database, a significant enrichment in cancer genes (such as MCL1, BCL2, ETS1, or JUN) that directly or indirectly affect apoptosis and cell cycle was found.",

keywords = "Cancer, MicroRNA, Targets",

author = "Calin, {George A.} and Amelia Cimmino and Muller Fabbri and Manuela Ferracin and Wojcik, {Sylwia E.} and Masayoshi Shimizu and Cristian Taccioli and Nicola Zanesi and Ramiro Garzon and Aqeilan, {Rami I.} and Hansjuerg Alder and Stefano Volinia and Laura Rassenti and Xiuping Liu and Liu, {Chang Gong} and Kipps, {Thomas J.} and Massimo Negrini and Croce, {Carlo M.}",

year = "2008",

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doi = "10.1073/pnas.0800121105",

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Calin, GA, Cimmino, A, Fabbri, M, Ferracin, M, Wojcik, SE, Shimizu, M, Taccioli, C, Zanesi, N, Garzon, R, Aqeilan, RI, Alder, H, Volinia, S, Rassenti, L, Liu, X, Liu, CG, Kipps, TJ, Negrini, M & Croce, CM 2008, 'MiR-15a and miR-16-1 cluster functions in human leukemia', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 13, pp. 5166-5171. https://doi.org/10.1073/pnas.0800121105

TY - JOUR

T1 - MiR-15a and miR-16-1 cluster functions in human leukemia

AU - Calin, George A.

AU - Cimmino, Amelia

AU - Fabbri, Muller

AU - Ferracin, Manuela

AU - Wojcik, Sylwia E.

AU - Shimizu, Masayoshi

AU - Taccioli, Cristian

AU - Zanesi, Nicola

AU - Garzon, Ramiro

AU - Aqeilan, Rami I.

AU - Alder, Hansjuerg

AU - Volinia, Stefano

AU - Rassenti, Laura

AU - Liu, Xiuping

AU - Liu, Chang Gong

AU - Kipps, Thomas J.

AU - Negrini, Massimo

AU - Croce, Carlo M.

PY - 2008/4/1

Y1 - 2008/4/1

N2 - MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression that play roles in human diseases, including cancer. Each miRNA is predicted to regulate hundreds of transcripts, but only few have experimental validation. In chronic lymphocytic leukemia (CLL), the most common adult human leukemia, miR-15a and miR-16-1 are lost or down-regulated in the majority of cases. After our previous work indicating a tumor suppressor function of miR-15a/16-1 by targeting the BCL2 oncogene, here, we produced a high-throughput profiling of genes modulated by miR-15a/16-1 in a leukemic cell line model (MEG-01) and in primary CLL samples. By combining experimental and bioinformatics data, we identified a miR-15a/16-1-gene signature in leukemic cells. Among the components of the miR-15a/16-1 signature, we observed a statistically significant enrichment in AU-rich elements (AREs). By examining the Gene Ontology (GO) database, a significant enrichment in cancer genes (such as MCL1, BCL2, ETS1, or JUN) that directly or indirectly affect apoptosis and cell cycle was found.

AB - MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression that play roles in human diseases, including cancer. Each miRNA is predicted to regulate hundreds of transcripts, but only few have experimental validation. In chronic lymphocytic leukemia (CLL), the most common adult human leukemia, miR-15a and miR-16-1 are lost or down-regulated in the majority of cases. After our previous work indicating a tumor suppressor function of miR-15a/16-1 by targeting the BCL2 oncogene, here, we produced a high-throughput profiling of genes modulated by miR-15a/16-1 in a leukemic cell line model (MEG-01) and in primary CLL samples. By combining experimental and bioinformatics data, we identified a miR-15a/16-1-gene signature in leukemic cells. Among the components of the miR-15a/16-1 signature, we observed a statistically significant enrichment in AU-rich elements (AREs). By examining the Gene Ontology (GO) database, a significant enrichment in cancer genes (such as MCL1, BCL2, ETS1, or JUN) that directly or indirectly affect apoptosis and cell cycle was found.

KW - Cancer

KW - MicroRNA

KW - Targets

UR - http://www.scopus.com/inward/record.url?scp=42449152333&partnerID=8YFLogxK

U2 - 10.1073/pnas.0800121105

DO - 10.1073/pnas.0800121105

M3 - Article

C2 - 18362358

AN - SCOPUS:42449152333

SN - 0027-8424

VL - 105

SP - 5166

EP - 5171

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 13

ER -

MiR-15a and miR-16-1 cluster functions in human leukemia

Abstract

Keywords

UN SDGs

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