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the findings that miR-203 is upregulated in psoriasis, a common human
hyperproliferative skin disease involving a proinflammatory response, and in
a few epithelial tumors ( Bandres et al ., 2006; Gottardo et al ., 2007; Iorio
et al ., 2007; Sonkoly et al ., 2007; Szafranska et al ., 2007 ). While further
studies will be necessary to reconcile these differences, one possibility is that
the expression of miR-203 can be independently induced under stress
conditions, for example, cancer, psoriasis, or other diseases, perhaps as a
negative and in some cases futile feedback mechanism to suppress the
proliferative state.
A final interesting twist to the possible tumor suppressive roles of miR-203
comes from recent studies on the human papillomaviruses (HPVs), which
do not encode their own miRs ( Cai et al ., 2006 ) but do modulate expression
of cellular miRNAs to regulate the activities of cellular proteins. Recently, it
was discovered that one of HPV's two oncoproteins, E7, downregulates
miR-203 expression upon epidermal differentiation ( Melar-New and
Laimins, 2010 ), while the other, E6, downregulates miR-203 by compromis-
ing p53 function ( McKenna et al ., 2010 ). Moreover, HPV-positive cells
maintain significantly higher levels of
than normal keratinocytes
do, andwhenmiR-203 was introduced into keratinocytes that stablymaintain
HPV episomes, the HPVwas rapidly lost upon subsequent passage. Together,
these findings suggest thatmiR-203 is inhibitory toHPVamplification and that
HPV oncoproteins act in part by suppressing miR-203 in differentiating cells
to disrupt the balance between proliferation and differentiation and allow
productive HPV replication and propagation.
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Np63
a
9. Characterizing and Defining the Functions
of Specific miRs that are Differentially
Expressed by HF Stem Cells
Most recently, a study for miR in HF stem cells provides another
dimension to miR function. MiR-125b, a lin-4 homologue, was identified
as a markedly upregulated miR in HF stem cells relative to any of the three
other proliferating compartments within the skin epithelium ( Zhang et al .,
2011 ). Moreover, as judged by in situ hybridizations, miR-125b rapidly
waned once stem cells exited their niche and became ORS progenitors.
Thereafter, miR-125b remained off as ORS cells progressed further to
become the matrix cells ( Zhang et al ., 2011 ).
To understand how this switch in miR-125b expression relates to the
ability of SCs to embark upon the HF lineage, Zhang and Fuchs took
a doxycycline (tetracycline) inducible, transgenic strategy and sustained
miR-125b expression in the proliferative progeny of HF-SCs. The outcome
was a shift in the balance between the stem cells and their committed progeny.
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