KDM3A, A NOVEL BLOOD-BASED BIOMARKER
IN COLORECTAL CARCINOGENESIS
Polat D.1, Onur E.2,*, Yılmaz N.3, Sökücü M.4, Gerçeker O.F.1
*Corresponding Author: Assoc. Prof. Elif Onur, Department of Medical Biology, Faculty of Medicine,
SANKO University, 27090 Gaziantep, Turkey; Phone:+90 342 211 6562; Fax: +90 342 211
6566; Email: elif.onur@sanko.edu.tr
page: 23
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INTRODUCTION
Colorectal cancer (CRC) is a leading cause of morbidity
and mortality throughout the world. It is the third most
frequent cancer among worldwide and the second most
common cause of death (1). Although the high incidence
and mortality have increased interest to better understand
the pathogenesis of CRC, the molecular mechanism which
triggers CRC progression is not clearly identified (2). Also,
determination of blood-based biomarkers for diagnosis
and treatment in CRC is one of the most studied subjects.
The HIF-1 gene is the key regulator of hypoxic cell
response and development of many cancer types. Hypoxiainducible
factor-1 (HIF-1) consists of two subunits: HIF-
1α and HIF-1β. Its construction is O2-dependent in the
nucleus. Under normoxia with adequate O2 conditions,
the HIF-1α subunit is degraded in the proteasome (3).
But under hypoxic conditions, this degradation pathway is
disrupted, and HIF-1α accumulates in the nucleus (4). The
HIF-1α function has been shown to influence particular Jumonji
C-domain-containing histone demethylases (JHDM)
(5, 6). These histone demethylases form a broad family of
enzymes, each of which has a specific ability to influence
transcriptional repression on specific histone residues (7).
KDM3A regulates the expressions of some pro-angiogenic
hypoxia dependent genes by reducing histone methylation
in promoters (8-10). Uemura et al. demonstrated the association
between KDM3A and CRC in human colon cancer
cell lines and tissue samples and this gene was indicated
to be a useful biomarker for hypoxic tumor cells and a
prognostic marker that could be a therapeutic target against
CRC (11). These data suggest a link between tumorigenesis
in the colon and KDM3A gene expression.
Early detection of CRC influences the survival rate
of patients (12). Colonoscopy is the gold standard for
the diagnosis of CRC; however, it is an invasive, time-consuming and expensive method (13). Therefore, it is
important to find an easily detectable, and non-invasive
blood-based biomarker for the early detection of CRC.
We aimed to evaluate whether the expression levels of
the KDM3A gene could be useful predictors of colorectal
carcinogenesis in circulation.
Epithelial-Mesenchymal Transition (EMT) ensures
a mechanism for cancer cells to obtain a more aggressive
phenotype which is controlled by several transcription
regulators, including E-cadherin, Claudin-1, Slug,
and ZEB-1. In the process of EMT, expression levels of
epithelial markers such as E-cadherin and Claudin-1 are
decreased, whereas those of mesenchymal markers such
as Slug, and ZEB-1 are increased (14). We investigated the
expression levels E-cadherin, Claudin-1, Slug, and ZEB-1
to determine this association.
In this study, it was determined that KDM3A is related
to CRC, and in our opinion, these results are very valuable
as this is the first expression study based on human
peripheral leukocyte samples that showed this association.
Based on this data, KDM3A is an important target in the
diagnosis in CRC.
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