Abstract
To date, more than 200 microRNAs have been described in humans; however, the precise functions of these regulatory, non-coding RNAs remains largely obscure. One cluster of microRNAs, the mir-17-92 polycistron, is located in a region of DNA that is amplified in human B-cell lymphomas. Here we compared B-cell lymphoma samples and cell lines to normal tissues, and found that the levels of the primary or mature microRNAs derived from the mir-17-92 locus are often substantially increased in these cancers. Enforced expression of the mir-17-92 cluster acted with c-myc expression to accelerate tumour development in a mouse B-cell lymphoma model. Tumours derived from haematopoietic stem cells expressing a subset of the mir-17-92 cluster and c-myc could be distinguished by an absence of apoptosis that was otherwise prevalent in c-myc-induced lymphomas. Together, these studies indicate that non-coding RNAs, specifically microRNAs, can modulate tumour formation, and implicate the mir-17-92 cluster as a potential human oncogene.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Line, Tumor
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Disease Models, Animal
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic*
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Genes / genetics*
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Genes, myc / genetics
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Humans
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Lymphoma, B-Cell* / genetics*
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Mice
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MicroRNAs / genetics*
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Molecular Sequence Data
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Multigene Family / genetics
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Oncogenes / genetics*
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Phenotype
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
Substances
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MicroRNAs
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
Associated data
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GENBANK/GSM45026
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GENBANK/GSM45027
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GENBANK/GSM45028
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GENBANK/GSM45029
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GENBANK/GSM45030
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GENBANK/GSM45031
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GENBANK/GSM45032
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GENBANK/GSM45033
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GENBANK/GSM45034
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GENBANK/GSM45035
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GENBANK/GSM45036
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GENBANK/GSM45037
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GENBANK/GSM45038
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GENBANK/GSM45039
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GENBANK/GSM45040
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GENBANK/GSM45041
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GENBANK/GSM45042
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GENBANK/GSM45043
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GENBANK/GSM45044
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GENBANK/GSM45045
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GENBANK/GSM45046
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GENBANK/GSM45047
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GENBANK/GSM45048
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GENBANK/GSM45049
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GENBANK/GSM45050
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GENBANK/GSM45051
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GENBANK/GSM45052
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GENBANK/GSM45053
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GENBANK/GSM45054
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GENBANK/GSM45055
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GENBANK/GSM45056
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GENBANK/GSM45057
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GENBANK/GSM45058
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GENBANK/GSM45059
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GENBANK/GSM45060
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GENBANK/GSM45061
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GENBANK/GSM45062
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GENBANK/GSM45063
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GENBANK/GSM45064
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GENBANK/GSM45065