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Gene & Protein in Disease RUNX1 gene in female-related cancers

KO of RUNX1 at exon 5 (ablating all three isoforms) did compartments in hair follicles, where the three RUNX
not affect the development of CD34+/CD31+/CD144+ proteins are expressed . The epithelial expression
[77]
endothelial-like cells. However, no CD45+ hematopoietic involves hair keratin, which forms layers of the hair shaft
cells developed from the endothelial-to-hematopoietic and the bulge. The RUNX1 gene is notably coexpressed
transition (EHT) culture that was treated with hematopoietic with keratin 15, which is a marker of hair follicle stem
cytokines, indicating that the EHT was fully inhibited . cells. RUNX1 gene is expressed in a distinct dermal sub-
[27]
epithelial layer in the hair mesenchyme during the initial
2.2.2. Nociceptive sensory neurons regulation stages of hair morphogenesis. At the same time, it is
The transduction of noxious stimuli triggers the located in the dermal papilla at later stages in a hair cycle-
interpretation of pain in mammals through specialized dependent pattern. In experiments on knockout mice, the
ion channels and receptors expressed by nociceptive RUNX1 gene was found to be expressed in several hair
[70]
sensory neurons . However, the molecular mechanisms follicle chambers, along with the bulge and germ, but not
responsible for specifying different sensory modalities in other skin epithelial structures, such as the sebaceous
remain poorly understood. RUNX1, a runt domain gland and the epidermis. The structure of the hair shaft, the
transcription factor, is expressed in most nociceptors activation of HFSC, and the onset of anagen are all affected
during embryogenesis. RUNX1 controls the expression by constitutive epithelial deletion of RUNX1 gene through
of several ion channels and receptors in these neurons, development. Besides, the role of RUNX1 gene in skin
[78]
namely, thermal receptors of the transient receptor potential cancers is yet to be explored . It is necessary to clarify this
(TRP) class, Na -gated, ATP-gated, and H -gated channels, stance because skin cancer is the most common human
+
+
μ-opioid receptor (MOR), and protein-coupled receptors of malignancy and HFSC is a well-recognized source of skin
Mas-related G-protein-coupled receptor (Mrgpr) class G . appendage tumors, such as basal cell carcinoma (Table 2).
[71]
RUNX1 also regulates the lamina-specific innervation
pattern of the spinal cord’s nociceptive afferents. In addition, 3. RUNX1 gene and female health
mice that lack RUNX1 show certain defects in thermal and 3.1. Sex determination
neuropathic pain , thus suggesting that the phenotype
[72]
is coordinated by RUNX1. This finding has implications Sex determination is the process through which sexually
[79]
for pain treatment of a broad cohort of nociceptors. reproducing organisms differentiate as male or female .
The mammalian genome encodes three runt domain Although the process varies extensively between different
transcription variables: RUNX1, RUNX2, and RUNX3. These organisms, numerous species have shown a physiological
runt proteins interact with CBFβ cofactor to regulate several link between the RUNX1 gene and the development of
female reproductive tissues. Conceivably, this link was
[73]
developmental processes . The trigeminal and dorsal root studied for the first time in Drosophila melanogaster. It can
ganglia both express RUNX1 and RUNX3. It appears that be seen that the runt gene is required to express Sxl or Sex-
RUNX1 expression is limited to nociceptors; the persistent lethal gene in the blastoderm embryo, which is responsible
RUNX1 gene expression labels nociceptors undergoing the for maintaining the on/female mode or off/male
developmental transition from TrkA to Ret. The transition mode [80,81] . In mammals, the RUNX1 gene was found to be
from TrkA to Ret is disrupted in mice that selectively lack strongly expressed in the ovarian stroma, suggesting that
RUNX1 gene function in the peripheral nervous system . it is indeed related to female sex development . RUNX1
[74]
[82]
Besides, we find that activating or suppressing the expression protein was also detected in oocytes and granulosa cells
of a significant number of nociceptive ion channels and of preantral follicles and theca cells of antral follicles. This
sensory receptors requires RUNX1 molecules.
was further bolstered by the fact that RUNX1 is a Wnt-4
Moreover, the RUNX1 gene is necessary for the signaling target gene . The absence of Wnt-4 results in
[83]
dorsal spinal cord to target afferent projections to the partial reverts of a female embryo into a male embryo.
specific lamina . Ultimately, behavioral research has In addition, Wnt-4 also suppresses testosterone-related
[75]
demonstrated certain deficits in thermal and neuropathic genes, promotes the maturation of the Mullerian duct, and
pain in RUNX1-deficient mice. These results indicate triggers the production of female germ cells. The knockout
that the phenotype of a broad collection of nociceptors is of Wnt-4 causes a reduction in RUNX1 gene expression,
coordinated by RUNX1 molecules . suggesting that the RUNX1 gene might play a crucial role
[40]
in ovary organogenesis . A significant expression of the
[84]
2.2.3. Hair follicle development RUNX1 gene in the ovaries of various species (human,
RUNX1 genes also regulate HFSC activation and goat, mice, and trout) during early gonad differentiation
proliferation in adult skin . RUNX1 gene expression indicates an evolutionarily conserved role of the gene in
[76]
is most common in the mesenchymal and epithelial ovary differentiation.

Volume 1 Issue 2 (2022) 5 https://doi.org/10.36922/gpd.v1i2.147