A miR Image of Stem Cells and Their Lineages - Current Topics in Developmental Biology - page 183

A B

SC
GL

Blim p 1

miR125b

Other
targets?

SL

VDR

SG
SC
ORS BL

Mx

IRS

BM

Expression

DP

SCD ACD

Figure 7.4 Two distinct models for miR's functions in skin stem cells. (A) Reciprocal
spatial expression of miR-203 and its target, p63, in the epidermis. In the basal
stem cells (BL), p63 is highly expressed to maintain the stemness. Upon differentiation,
miR-203 is rapidly upregulated to repress p63 expression in the suprabasal layers
including spinous (SL) and granular (GL) layers. (B) miR-125b fine-tunes the input
of hair follicle stem cells into sebaceous gland and hair follicle lineages by targeting
Blimp1 and VDR, respectively.

case, the exit of somatic stem cell cycling and the induction of terminal
differentiation appeared to be regulated by distinct mechanisms. This model
is in a close agreement with the paradigm established by the lin-4 and let-7
studies in C. elegans where miRs function to promote developmental
transitions by inhibiting key molecules that are required for early develop-
mental stages, but which must later be downregulated to progress through
the differentiation program.

8. miR-203 as a Tumor Suppressor?

Because of the potent inhibition of miR-203 to cell proliferation,
miR-203 might be expected to function as a tumor suppressor. Indeed,
miR-203 was induced in a head and neck squamous cell carcinoma cell line
exposed to UVC irradiation, a treatment that results in cell death and cell
cycle exit ( Lena et al ., 2008 ). Conversely, an elegant study in human
hematopoietic tumors revealed that frequent silencing of miR-203 either
genetically or epigenetically is correlated with T cell lymphomas ( Bueno
et al ., 2008 ). Moreover, forced expression of miR-203 directly resulted in
the downregulation of the oncogene, BCR-ABL1, and blocked cancer cell
proliferation ( Bueno et al ., 2008 ). Oddly, however, and in contrast to the
epidermis, miR-203 is not detected in normal T cell lineages ( Landgraf
et al ., 2007; Neilson et al ., 2007; Wu et al ., 2007 ). Even more paradoxical are