miR-19 is a key oncogenic component of mir-17-92.

By V. Olive, M. Bennett, James C. Walker, Cong Ma, Iris Jiang, C. Cordon-Cardo, Qi-jing Li, Scott W. Lowe, Gregory J. Hannon, Lin He. Genes & Development, 2009

639 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a9b3ea73c8b50c08e5df9575adc9bf2ba95744bb

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Citations in the corpus

Desperately seeking microRNA targets (2010, background): “Conditional overexpression of each of the six miRNAs in the oncogenic miR-17–92 cluster pinpointed a prominent role for miR-19, which largely recapitulated the oncogenic properties of the cluster, in hematological cancers in vitro and in vivo”
Targeting MicroRNAs in Cancer: Rationale, Strategies and Challenges (2010, neutral): “The authors discovered that overexpressing the whole cluster, the cluster without mir-92 , but not the cluster lacking mir-19a or mir-19b , promotes oncogenesi”
Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs (2011, positive): “…Berger et al., 2011; Trotman et al., 2003), and (3) numerous microRNAs have beenvalidatedasPTENregulators, including theproto-oncogenic miR-106b 25 cluster that is overexpressed in prostate cancer (Huse et al., 2009; Mu et al., 2009; Olive et al., 2009; Poliseno et al., 2010a; Xiao et al., 2008).”
MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy (2011, positive): “Of the three, the miR-19 family has been confirmed by two groups to contain the key oncomir”
microRNAs in cancer (2013, background): “Retroviral overexpression of the cluster accelerated Myc-induced lymphoma formation (62), and in vivo dissection of the cluster’s activity demonstrated that miR-17/92 tumorigenic activity depends on the presence of the miR-19 seed family (74, 75).”