Research articles
ScienceAsia 48 (2022):ID 518-523 |doi:
10.2306/scienceasia1513-1874.2022.073
Overexpression of HMGN3 nucleosome binding protein is
associated with tumor invasion and TGF-β expression in
cholangiocarcinoma
Supannika Sorina,b, Nongnapas Pokaewa, Kulthida Vaeteewoottacharna, Sakda Waraasawapatic, Chawalit Pairojkulc, Goro Sashidad, Kanlayanee Sawanyawisutha,b,*
ABSTRACT: High mobility group nucleosome binding (HMGN) protein is a non-histone protein that affects the
chromatin function, leading to the regulation of gene expression. Several studies reported the aberrant expression
of HMGN1?HMGN5 in variety of cancers. This study aimed to investigate a potential HMGN protein and its clinical
impact in cholangiocarcinoma (CCA). Analysis of gene expression profiles of HMGNs in liver cancers from public
database demonstrated the alteration of HMGN1?HMGN5 in CCA and hepatocellular carcinoma (HCC) tissues. HMGN3
was the only member that overexpressed in CCA, but not HCC, and hence was selected for further study. The
immunohistochemistry of HMGN3 revealed that HMGN3 was weakly detected in normal bile ducts and hepatocytes
but was gradually expressed in hyperproliferative bile ducts and CCA tissues, indicating the involvement of HMGN3 in
development and progression of CCA. CCA exhibited significantly higher expression of HMGN3 than HCC, suggesting
HMGN3 as a diagnostic marker distinguishing CCA from HCC. Univariate analysis revealed the association of high
HMGN3 expression and tumor invasion of CCA patients. The expression of transforming growth factor ? (TGF-?), a
major inflammatory cytokine related to liver fluke-related CCA, was positively correlated with the expression of HMGN3
in CCA tissues. Treating CCA cell lines with recombinant TGF-?1 significantly induced the mRNA expression of HMGN3
but not the cholangiocytes. This finding signifies the positive correlation of TGF-?1 and HMGN3 observed in CCA
tissues and the influence of TGF-?1 on HMGN3 expression. Further mechanistic studies are necessary to validate these
findings.
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| a |
Department of Biochemistry, and Center for Translational Medicine, Faculty of Medicine, Khon Kaen University,
Khon Kaen 40002 Thailand |
| b |
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002 Thailand |
| c |
Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 Thailand |
| d |
Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences
(IRCMS), Kumamoto University, Kumamoto 860-0811 Japan |
* Corresponding author, E-mail: kanlayanee@kkumail.com
Received 20 Jan 2022, Accepted 3 Mar 2022
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