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

related deaths in women worldwide [124,125] . Moreover, 5.4. Cervical cancer: Overview and development
around 300,000 new cases of ovarian cancer occur every Cervical cancer rates vary across the world, with Eastern
year according to the World Cancer Research Fund [126] . Africa having the highest rate and Western Asia having
Most tumors in this particular malignancy are usually the lowest. According to the WHO, it is the fourth most
diagnosed at a very late stage when patients present with common type of cancer in women and a major cause of
upper abdominal and distant metastases. In such cases, cancer-related deaths among low- and middle-income
life-saving surgery cannot be performed [127] . The disease countries. In 2020, an estimated 604,237 women were
may be caused by various genes being overexpressed,
under-expressed, or even subjected to epigenetic changes diagnosed with cervical cancer globally, representing 6.5%
[131]
besides somatic mutations [128] . In a study, hypomethylation of all female cancers ; new cases of cervical cancer have
was observed in 46 putative oncogenes in the primary been estimated to be around 14,100 in 2022, with 4280
[132]
cell culture, where a high occurrence of RUNX1 deaths . One of the significant kinds of adenocarcinoma,
mutation was detected in ovarian cancer progression . developed from the influence of RUNX1, is the cervical
[3]
Immunohistochemical analysis showed that RUNX1 gene that occurs in the ectocervix. In the lower Mullerian duct
expression was significantly higher in high malignant (MD), epithelial cells are obligated to become stratified
potential and low malignant potential tumors, as well as in squamous epithelium of the ectocervix and vagina, as the
omental metastasis, compared to normal ovary . Another expression of ΔNp63 transcription factor is induced by
[34]
report demonstrated that short hairpin (sh)RNA-mediated vaginal mesenchyme [111] . In the MD epithelium (MDE),
RUNX1 knockdown significantly impacted the proliferative SMAD4 gene is essential for the activation of ΔNp63. This
and migratory ability of ovarian cancer-causing SKOV3 cells transcription factor binds on the 5′ sequence adjacent to
(Figure 6). Similarly, RUNX1 mRNA upregulation and the transcription start site (TSS) of ΔNp63 in the future
RUNX1 protein overexpression are known to decrease miR- vaginal epithelium (VgE) [133] . This SMAD-dependent
302b and increase the risk of ovarian cancer [110] . A reduced activation of the ΔNp63 locus requires the expression
miR-302b can regulate RUNX1 pro-oncogenic activity, of RUNX, which activin A (ActA) activates through a
leading to signal transducer and activator of transcription SMAD-independent mechanism [134] . The ActA-RUNX1
3 (STAT3) signaling pathway [129] . Likewise, in the case of pathway is independently required for the vaginal cell
ovarian cancer, it can have the same effect by activating fate commitment of MDE. Inactivation of it in MDE
invasive phenotypes by MMP-2 and MMP-9 signaling results in uterine epithelial differentiation of MDE within
pathways [130] . Therefore, all the dysfunctional evidence the vagina, a congenital epithelial lesion called vaginal
hints at the correlation between the oncogenic functionality adenosis [133] . Vaginal adenocarcinomas (VACs) or cervical
of RUNX1 gene and a potential prognostic biomarker cancers are believed to arise from vaginal adenosis due to
for developing ovarian cancer in the female population. adenosis lesions at the primary site of VACs [135] . According
A carcinoma cell biopsy followed by immunohistochemical to cBioPortal for Cancer Genomics, the RUNX1 gene
analysis revealed significant upregulation of the RUNX1 shows 2.3% genetic perturbations in cervical cancers. In
gene compared to the control, suggesting the use of RUNX1 their report, the genetic alterations of RUNX1, including
gene as a biomarker for ovarian cancer diagnosis . amplification of 1%, deep deletion of 2%, and missense
[3]

Figure 6. Formation of ovarian cancer by different mutated pathways of RUNX1.

Volume 1 Issue 2 (2022) 10 https://doi.org/10.36922/gpd.v1i2.147