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miR-20a and miR-290, multi-faceted players with a role in tumourigenesis and senescence.

Rizzo M, Mariani L, Pitto L, Rainaldi G, Simili M - J. Cell. Mol. Med. (2010)

Bottom Line: Expression of microRNAs changes markedly in tumours and evidence indicates that they are causatively related to tumourigenesis, behaving as tumour suppressor microRNAs or onco microRNAs; in some cases they can behave as both depending on the type of cancer.The INK4a/ARF locus which codifies for two proteins, p19ARF and p16INK4a, plays a central role in senescence by controlling both p53 and RB.Intriguingly, both miR-20a, member of the oncogenic miR-17-92 cluster, and miR-290, belonging to the miR-290-295 cluster, are highly expressed in embryonic stem (ES) cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Gene and Molecular Therapy, Institute of Clinical Physiology, CNR, Pisa, Italy.

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MiR-290–295 cluster is causatively involved in MEF senescence. MiR-290–295 cluster induces senescence by activating the INK4a/ARF locus. Possible mechanisms are: (i) LRF down-regulation with activation of p19ARF and p53 and (ii) p16INK4a up-regulation by EZH2 down-regulation. Other candidate targets are members of the MAPK family, among which MAPK1/ERK1, known to activate cell proliferation. The induction of p16INK4a by miR-20a (see Fig. 2C) could be mediated by miR-290–295 cluster.
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fig03: MiR-290–295 cluster is causatively involved in MEF senescence. MiR-290–295 cluster induces senescence by activating the INK4a/ARF locus. Possible mechanisms are: (i) LRF down-regulation with activation of p19ARF and p53 and (ii) p16INK4a up-regulation by EZH2 down-regulation. Other candidate targets are members of the MAPK family, among which MAPK1/ERK1, known to activate cell proliferation. The induction of p16INK4a by miR-20a (see Fig. 2C) could be mediated by miR-290–295 cluster.

Mentions: A recurrent result found in culture-induced senescent MEF is the consistent association between miR-290 up-regulation and the increased expression of the INK4a/ARF locus (p19ARF and mainly p16INK4a) [42]. It has been shown that the increase of p16INK4a and to a lesser extent that of p19ARF observed during senescence in primary fibroblast (including MEF) is due to down-regulation of EZH2, part of the PRC2 complex which inhibits the INK4a/ARF locus [58]. In silico analysis and preliminary experiments utilizing a gene reporter assay indicate that the 3′UTR of murine EZH2 is a target of miR-290 (Rainaldi G., unpublished data). Future studies will establish whether EZH2 down-regulation during MEF senescence is causatively connected to miR-290 up-regulation; if this were the case p16INK4a increase observed after miR-20a overexpression [41] could be miR-290 dependent (Fig. 3).


miR-20a and miR-290, multi-faceted players with a role in tumourigenesis and senescence.

Rizzo M, Mariani L, Pitto L, Rainaldi G, Simili M - J. Cell. Mol. Med. (2010)

MiR-290–295 cluster is causatively involved in MEF senescence. MiR-290–295 cluster induces senescence by activating the INK4a/ARF locus. Possible mechanisms are: (i) LRF down-regulation with activation of p19ARF and p53 and (ii) p16INK4a up-regulation by EZH2 down-regulation. Other candidate targets are members of the MAPK family, among which MAPK1/ERK1, known to activate cell proliferation. The induction of p16INK4a by miR-20a (see Fig. 2C) could be mediated by miR-290–295 cluster.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373484&req=5

fig03: MiR-290–295 cluster is causatively involved in MEF senescence. MiR-290–295 cluster induces senescence by activating the INK4a/ARF locus. Possible mechanisms are: (i) LRF down-regulation with activation of p19ARF and p53 and (ii) p16INK4a up-regulation by EZH2 down-regulation. Other candidate targets are members of the MAPK family, among which MAPK1/ERK1, known to activate cell proliferation. The induction of p16INK4a by miR-20a (see Fig. 2C) could be mediated by miR-290–295 cluster.
Mentions: A recurrent result found in culture-induced senescent MEF is the consistent association between miR-290 up-regulation and the increased expression of the INK4a/ARF locus (p19ARF and mainly p16INK4a) [42]. It has been shown that the increase of p16INK4a and to a lesser extent that of p19ARF observed during senescence in primary fibroblast (including MEF) is due to down-regulation of EZH2, part of the PRC2 complex which inhibits the INK4a/ARF locus [58]. In silico analysis and preliminary experiments utilizing a gene reporter assay indicate that the 3′UTR of murine EZH2 is a target of miR-290 (Rainaldi G., unpublished data). Future studies will establish whether EZH2 down-regulation during MEF senescence is causatively connected to miR-290 up-regulation; if this were the case p16INK4a increase observed after miR-20a overexpression [41] could be miR-290 dependent (Fig. 3).

Bottom Line: Expression of microRNAs changes markedly in tumours and evidence indicates that they are causatively related to tumourigenesis, behaving as tumour suppressor microRNAs or onco microRNAs; in some cases they can behave as both depending on the type of cancer.The INK4a/ARF locus which codifies for two proteins, p19ARF and p16INK4a, plays a central role in senescence by controlling both p53 and RB.Intriguingly, both miR-20a, member of the oncogenic miR-17-92 cluster, and miR-290, belonging to the miR-290-295 cluster, are highly expressed in embryonic stem (ES) cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Gene and Molecular Therapy, Institute of Clinical Physiology, CNR, Pisa, Italy.

Show MeSH
Related in: MedlinePlus