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

Table 1. List of some cancer types where RUNX1 gene RUNX1 gene may lead to constitutive gene abnormalities
functions as an oncogene or tumor suppressor gene. and, thus, result in tumorigenesis [53] , but RUNX1 gene
amplification induces gene overexpression or upregulation,
Function of Cancer type References
RUNX1 gene which has an immense potential to contribute to the
[54]
Oncogenic Triple-negative breast cancer [44,48,49] transformation of hematopoietic cells into tumors .
Ovarian cancer [34,48,55] 2.2.1. Hematopoiesis
Uterine cancer [47] Hematopoiesis occurs during embryonic development
Cervical cancer [47,55] and maturity to create and replenish the blood system.
Prostate cancer [47,48] Through hematopoiesis research, the mechanisms that
Colorectal cancer [47,48] lead to blood diseases and malignancies can be better
Skin cancer [48,55] understood by scientists and doctors. HSCs can also be
Head and neck cancer [48,56] utilized as a model system to study tissue stem cells and
their involvement in aging and cancer . HSCs form in the
[66]
Acute myeloid leukemia [44,57] human embryo at 1 month of gestation . However, before
[67]
Tumor Breast cancer (excluding triple negative) [48,58] HSCs appear, numerous other blood cells develop, some of
suppressor Gastrointestinal cancer [48,59] which are required for embryonic survival and contribute
Lung adenocarcinomas [48,60] to tissue macrophages in adults. HSCs and hematopoietic
Non-small cell lung cancer [48,49] progenitors (cells that can develop into various blood cells
Glioblastoma multiforme [48,61] but do not have long-term multiline age reconstitution
capability) arise in three waves, as detailed below. RUNX1
Hepatocellular carcinoma [54,62,63] gene is required to differentiate all embryonic blood
Acute lymphoblastic leukemia [64,65] cell lineages, but it plays a particularly important role in
differentiating blood cells from hemogenic endothelium in
[68]
Although the genes associated with cancer development the second and third waves .
are generally either tumor suppressor genes or oncogenes, Human embryonic stem cells (ESCs) and induced
the RUNX1 gene can function as both, depending on pluripotent stem cells (iPSCs) have been used to study
the context [42-44] . RUNX genes play a significant role as human hematopoiesis, including the involvement of
tumor suppressor genes by inactivating gene mutations, RUNX1 gene, over the past decade. In a study, human
hypermethylation, and deletions in some cancers [42,45] . CD34+ CD45+ hematopoietic stem and progenitor
While in many other cases, these genes are transcriptionally cells (HSPCs) were produced from human ESCs and
activated by retroviral insertion, indicating dominant iPSCs about 11–14 days following embryoid body (EB)
oncogenic potential [42,46] . The role of RUNX1 gene in formation using a feeder-free culture method. Multiple
tumorigenesis differs with the tumor tissue, type, and stage kinds of hematopoietic cells, including myeloid, erythroid,
of tumor development [44,47] . For instance, the RUNX1 gene and polyploid megakaryocytic (MK) cells, were formed by
plays the role of a tumor promoter in ovarian and skin CD34+ CD45+ HSPCs. The human iPSCs generated from
cancers , but it has been identified as a tumor suppressor familial platelet disorder (FPD) patients with heterozygous
[48]
in breast (excluding triple negative) , lung , and prostate RUNX1 mutation were similarly found to be deficient in
[49]
[48]
cancers [48,50] . RUNX1 mutations, which are mostly loss-of- MK production, with the targeted repair of the mutant
function mutations occurring due to non-sense, frame RUNX1 allele by genome editing restoring MK potential .
[69]
shift, or missense mutations within the runt DNA-binding Since then, scientists have expanded their research
[8]
domain , take place almost exclusively in the ER-positive, using precise genomic targeting in human wildtype iPSCs
luminal subtype of breast cancer, and pointing to a tumor to remove excess exon 5 of the RUNX1 gene, shared by all
[35]
suppressor role . three isoforms, or exon 1B, which is unique to the RUNX1c
On the contrary, enhanced levels of RUNX1 gene isoform. On days 11–14 following EB development, the
expression have been found to be associated with poor bi-allelic knockout (KO) of RUNX1 at exon 5 prevented
outcomes in triple-negative breast cancers (TNBCs), the production of hematopoietic cells. In the presence
suggesting its role as an oncogenic gene in this breast cancer of RUNX1a and RUNX1b isoforms, produced from the
subtype . Whether the RUNX1 gene acts as an activator downstream P2 promoter, the complete deletion of exon
[51]
or repressor of target gene expression, it depends on the 1B had no effect, thus revealing that the RUNX1c isoform
massive number of interacting coactivators, transcription is not required for definitive hematopoiesis. According to
factors, and corepressors . The downregulation of the a detailed examination of EBs on days 6–8, the bi-allelic
[52]

Volume 1 Issue 2 (2022) 4 https://doi.org/10.36922/gpd.v1i2.147