Page 31 - GPD-1-2

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

cancer can directly impair natural killer cell activity. Both hematopoietic and non-hematopoietic cancer cells can form
and become tumors when the RUNX1 gene is mutated, with female malignancies being the primary target. Therefore,
more research on RUNX1 gene’s pattern of expression, both in vitro and in silico, is needed to lower the incidence of
female-related cancers.

Keywords: RUNX1; Chromosomal translocation; Breast cancer; Uterine cancer; Ovarian cancer; Cervical cancer

1. Introduction the function of specific genes. This protein interacts with
the core-binding factor subunit beta or CBFβ (produced
Cancer is a disease where cells grow uncontrollably and from the CBF-β gene), which, in turn, helps connect it to
spread throughout the body, affecting the body’s immune DNA and inhibits DNA from being degraded (Figure 1).
system and eventually all the organs . Gynecologic cancer These proteins, collectively, form one version of a CBF [11-13] .
[1]
is any cancer that begins in a woman’s reproductive organs. The RUNX1 protein turns on genes that help control blood
Cervical, ovarian, uterine, vaginal, and vulvar cancers are cell growth (hematopoiesis) . Most research related to
[14]
the five most common kinds of gynecologic cancers . females (including breast, ovarian, uterine, and cervical
[2]
According to the data obtained from Cancer Research UK malignancies) indicates a prevalence of RUNX1 gene
in 2016, breast cancer is the most common female-related changes in hormone-associated cancers . Mutation in
[15]
cancer in women and has the second highest mortality the RUNX1 gene is often found in various hematological
rate; uterine cancer is the fourth most common cancer malignancies. With the advent of technological revolution,
in females and has the ninth highest mortality rate in RUNX1 mutation has been proven to play a more pervasive
women; ovarian cancer is the fifth most common cancer role in cancer than previously believed. Dysregulation
in women and the sixth most common cause of death in of the RUNX1 gene has been reported to be associated
women . According to the National Cancer Institute, the with gastric and hepatocellular carcinoma, while single
[3]
estimated number of new breast cancer cases and uterine nucleotide polymorphisms (SNPs) in RUNX1 have been
cancer cases in 2022 is 287,850 and 65,950, respectively, [3,15-21]
while the estimated deaths of these cases in 2022 are linked with human colorectal and prostate cancer .
43,250 and 12,550, respectively . The top four cancer- In almost 15% of esophageal cancers, RUNX1 mutation
[4]
related causes of death in females are expected to see a tended to be an essential factor for the etiology and
shift over the next two decades to lung (34,000 deaths), development of squamous cell carcinoma in the skin and
breast (30,000 deaths), pancreatic (22,000 deaths), and oral cavity; additionally, strongly focal RUNX1 deletions
[22]
uterine (18,000 deaths) by 2040 . Cancer diagnostics have been reported .
[5]
and treatments remain a challenge, because cancer RUNX1 gene was first discovered in acute myeloid
consists of a group of several diseases, and many diverse leukemia gene 1 (AML1) in 1991 as it was linked to the
genetic abnormalities underpin more than 200 different translocation of AML . Later in 1993, a murine version
[23]
[6]
mutations . Female-related cancers are caused by several of RUNX1 was discovered, leading to the development
[24]
factors, which can be genetic, epigenetic, viral, and of RUNX1 knockout mouse models . In a screen that
environmental . Among the susceptible genes, RUNX1 was performed to identify mutations affecting segment
[7]
is crucial as it has been found to be associated with most number and polarity in Drosophila, Nusslein-Volhard and
[25]
[8]
female-related cancers . The RUNX family of transcription Wieschaus identified the transcription factor RUNX .
factors is evolutionarily conserved proteins that play The mutation that led to defects in pre-segmentation
an essential role in fundamental biological processes,
including growth and development . There are three
[9]
members (RUNX1, RUNX2, and RUNX3) of the RUNX
transcription family in humans, each of which is uniquely
expressed in different tissues . The RUNX1 gene codes for
[10]
a human protein, a transcription factor called runt-related
transcription factor 1, is also known as acute myeloid
leukemia (AML) 1 or core-binding factor subunit alpha-
2, which regulates the differentiation of hematopoietic Figure 1. RUNX1 heterodimerization with its binding partner, CBF, and
stem cells (HSCs) into mature blood cells . The RUNX1 interaction with DNA at promoters of target genes that have the particular
[11]
protein binds to specific DNA regions and helps control binding site YGYGGTY, where Y is C or T.

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