title: Preliminary mechanism on the methylation modification of Dkk-1 and Dkk-3 in hepatocellular carcinoma.
abstract: Wnt/β-catenin signaling pathway, having a crucial role in regulating diverse cellular processes, can be a new therapeutic target in cancer. To investigate the role of Dkk-1 (Dickkopf-1) and Dkk-3 in tumors and cirrhoses of the liver tissue in hepatocellular carcinoma (HCC), tissues from 38 patients with HCC resections including 5 patients who underwent hemangioma surgery of adjacent tumor tissues at the same time were obtained. Tissues were divided into three groups (nonfibrosis, cirrhosis, and carcinoma) through hematoxylin-eosin (HE) staining. Methylation-specific polymerase chain reaction (PCR) (MSP) measured the methylation status, and reverse transcription-PCR tested the messenger RNA (mRNA) levels, and immunohistochemical analysis provided levels of protein expression. The methylation detection rate of Dkk-1 and Dkk-3 was the highest (P < 0.05) and the mRNA levels of Dkk-1 and Dkk-3 were the lowest (P < 0.05) in the carcinoma tissues. The mRNA levels of β-catenin were significantly higher in the carcinoma tissue than the other tissues (P < 0.05). The expression of Dkk-1 and Dkk-3 was significantly higher in the carcinoma tissues than the other tissues (P < 0.05); but the β-catenin expression was the highest (P < 0.05). Compared with the control, the mRNA levels of β-catenin in the Dkk-1 and Dkk-3 silencing cells increased 5.34 (P < 0.05) and 3.5 times (P > 0.05). After the interference of 5-aza-2'-deoxycytidine, the mRNA levels of Dkk-1 and Dkk-3 significantly increased 58.9 and 59.3 times (P < 0.0001), and the mRNA levels of β-catenin decreased 6.02 times (P < 0.05). In the process of HCC, the abnormal activity of Wnt/β-catenin signaling may be associated with the methylation of Dkk-1 and Dkk-3.
authors.affiliation: West China Hospital of Sichuan University, Chengdu, People's Republic of China, lianglibo1234567@126.com.
authors.forename: Libo
authors.initials: L
authors.lastname: Liang
authors.forename: He
authors.initials: H
authors.lastname: He
authors.forename: Ruixue
authors.initials: R
authors.lastname: Lv
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Henjian
authors.initials: H
authors.lastname: Huang
authors.forename: Zhenmei
authors.initials: Z
authors.lastname: An
authors.forename: Shuangqing
authors.initials: S
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018925:Chemokines; D019175:DNA Methylation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C501126:DKK1 protein, human; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D051176:beta Catenin