PMID- 20008935
OWN - NLM
STAT- MEDLINE
DCOM- 20091231
LR  - 20220330
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 23
IP  - 24
DP  - 2009 Dec 15
TI  - miR-19 is a key oncogenic component of mir-17-92.
PG  - 2839-49
LID - 10.1101/gad.1861409 [doi]
AB  - Recent studies have revealed the importance of multiple microRNAs (miRNAs) in 
      promoting tumorigenesis, among which mir-17-92/Oncomir-1 exhibits potent 
      oncogenic activity. Genomic amplification and elevated expression of mir-17-92 
      occur in several human B-cell lymphomas, and enforced mir-17-92 expression in 
      mice cooperates with c-myc to promote the formation of B-cell lymphomas. Unlike 
      classic protein-coding oncogenes, mir-17-92 has an unconventional gene structure, 
      where one primary transcript yields six individual miRNAs. Here, we functionally 
      dissected the individual components of mir-17-92 by assaying their tumorigenic 
      potential in vivo. Using the Emu-myc model of mouse B-cell lymphoma, we 
      identified miR-19 as the key oncogenic component of mir-17-92, both necessary and 
      sufficient for promoting c-myc-induced lymphomagenesis by repressing apoptosis. 
      The oncogenic activity of miR-19 is at least in part due to its repression of the 
      tumor suppressor Pten. Consistently, miR-19 activates the Akt-mTOR (mammalian 
      target of rapamycin) pathway, thereby functionally antagonizing Pten to promote 
      cell survival. Our findings reveal the essential role of miR-19 in mediating the 
      oncogenic activity of mir-17-92, and implicate the functional diversity of 
      mir-17-92 components as the molecular basis for its pleiotropic effects during 
      tumorigenesis.
FAU - Olive, Virginie
AU  - Olive V
AD  - Division of Cellular and Developmental Biology, Department of Molecular and Cell 
      Biology, University of California at Berkeley, Berkeley, California 94705, USA.
FAU - Bennett, Margaux J
AU  - Bennett MJ
FAU - Walker, James C
AU  - Walker JC
FAU - Ma, Cong
AU  - Ma C
FAU - Jiang, Iris
AU  - Jiang I
FAU - Cordon-Cardo, Carlos
AU  - Cordon-Cardo C
FAU - Li, Qi-Jing
AU  - Li QJ
FAU - Lowe, Scott W
AU  - Lowe SW
FAU - Hannon, Gregory J
AU  - Hannon GJ
FAU - He, Lin
AU  - He L
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R00 CA126186/CA/NCI NIH HHS/United States
GR  - R00 CA126186-04/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (MicroRNAs)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
SB  - IM
CIN - Genes Dev. 2010 Jan 1;24(1):1-4. PMID: 20047995
MH  - Animals
MH  - B-Lymphocytes/cytology/*metabolism
MH  - Cell Survival
MH  - Gene Expression Regulation, Neoplastic
MH  - Lymphoma/*metabolism/pathology
MH  - Mice
MH  - MicroRNAs/*metabolism
MH  - NIH 3T3 Cells
MH  - Oncogene Protein v-akt/metabolism
MH  - Oncogenes/*physiology
MH  - PTEN Phosphohydrolase/metabolism
MH  - Protein Kinases/metabolism
MH  - TOR Serine-Threonine Kinases
PMC - PMC2800084
EDAT- 2009/12/17 06:00
MHDA- 2010/01/01 06:00
PMCR- 2010/06/15
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/01/01 06:00 [medline]
PHST- 2010/06/15 00:00 [pmc-release]
AID - 23/24/2839 [pii]
AID - 10.1101/gad.1861409 [doi]
PST - ppublish
SO  - Genes Dev. 2009 Dec 15;23(24):2839-49. doi: 10.1101/gad.1861409.