Alteration of oncogenic IGF-Ⅱ gene methylation status associates with hepatocyte malignant transformation.pdf

Hepatobiliary & Pancreatic Diseases International 18(2019)158-163
Contents lists available at Sciencedirect
Hepatobiliary
HBPD
Pancreatic Diseases
Hepatobiliary Pancreatic Diseases International
International
ournalhomepagewww.elsevier.com/locate/hbpd
Original Article/Liver
Alteration of oncogenic IGF-IL gene methylation status associates with
hepatocyte malignant transformation
Bo-jun Tai, Min Ya0 Wen-jie Zheng, Yu-cheng Shen, Li Wang, Jian-ying Sun
Department of Infectious Diseases, Alated Hospi of Nantong University, Nantong 226001, Chin
Department of Immunology, Medical School of Nantong University, Nantong 226001, China
Department of Oncology, Afiliated Hospital of Nantong University, Nantong 226001, China
Department of Oncology, Afiliated Haian Hospital of Nantong University, Nantong 226601, China
A RT C E IN O
A B S TRA C T
Article history
Background: Oncogenic insulin-like growth factor-ii(igf-i)is overexpressed in hepatocellular carcinoma
Received 14 June 2018
the dynamic alteration of IGF-I CPG site methylation status
Accepted 31 December
and its molecular mechanism in HCC progre
Available online 21 Janu
019
IGF-I alterations were observed
It hepatocarcino
dels induced by
2-acetylaminofluorene. Liver IGF-I expression was compared by immunohistochemistry or tissue IGF-I
hepatocellular carcinoma
specific concentration( nmol/mg protein . Status of human IGF-I promoter 3(P3 )or rat IGF-L P2 CPG site
Insulin-like growth factor-il
methylation was amplified by methylation-specific polymerase chain reaction(MSP). Serum IGF-II levels
Hy
were quantitatively detected by an enzyme-linked immunosorbent assay
Methylation-specific PCR
Results: The levels of hepatic IGF-IL expression were significantly elevated in the HCC group(P<0.001)
Promoter
Molecular mechanism
The unmethylation rate of IGF-1 P3 CPG sites was 100% in the HCC-, 52. 5% in the paracancerous-, and
none (0% )in the distal noncancerous-tissues Abnormal IGF-I expression was related to differentiation
degree, tumor invasion, and positive HBV-DNA(all P* 0.001), with a negative correlation between P3
methylation degree and IGF-IL expression. There was a positive correlation between liver IGF-II spec
concentration and circulating IGF-LL level(r=0.97, P<0.001). Significantly negative correlation was found
between IGF-L P CPG site methylation and circulatin IGF-I(s=-0.89, P<0.001 )or liver IGF-I level
Conclusions: The increase of serum IGF-I and the alteration of onc
gene IGF-L methylation may be
biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC
o 2019 First Afiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier
B V. All rights reserved
ntroduction
new circulating tumor cells, key signal molecules, long non-coding
RNA, and MICRORNA are the potential markers for monitoring
Hepatocellular carcinoma(HCC)ranks the sixth most common HCC 6. DNA cytosine methylation status, a central epigenetic
cancer and the second leadin cause of cancer mortality world-modification in cellular processes 7 is closely associated with the
wide. HCC is still one of the most common tumors in China, es-development and progression of HCC 8]. Oncogenic insulin-like