Genetic alterations of Wnt signaling pathway-associated genes in hepatocellular carcinoma

2007 ◽  
Vol 23 (1) ◽  
pp. 110-118 ◽  
Author(s):  
Young-Dae Kim ◽  
Chang-Hwan Park ◽  
Hyun-Soo Kim ◽  
Sung-Kyu Choi ◽  
Jong-Sun Rew ◽  
...  
2019 ◽  
Vol 51 (11) ◽  
pp. 1-20 ◽  
Author(s):  
Jun-Cheng Guo ◽  
Yi-Jun Yang ◽  
Jin-Fang Zheng ◽  
Jian-Quan Zhang ◽  
Min Guo ◽  
...  

AbstractHepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.


2017 ◽  
Vol 38 (4) ◽  
pp. 2351-2359 ◽  
Author(s):  
Chunlin Jiang ◽  
Miao Yu ◽  
Xiaoyan Xie ◽  
Guangliang Huang ◽  
Yao Peng ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Surbhi Chouhan ◽  
Snahlata Singh ◽  
Dipti Athavale ◽  
Pranay Ramteke ◽  
Vimal Pandey ◽  
...  

2021 ◽  
Author(s):  
Xuejing Lin ◽  
Ziming Mao ◽  
Lei Chen ◽  
Haihua Qian ◽  
Chunying Liu ◽  
...  

Abstract Background: Reversible phosphorylation and dephosphorylation play important roles in cell function and cell signal transduction. PPP2R5A is responsible for specifically regulating the catalytic function, substrate specificity and intracellular localization of the tumor suppressor phosphatase PP2A. Therefore, the abnormal expression and function of PPP2R5A may be related to the occurrence and development of tumors.Results: This study showed that PPP2R5A inhibited the proliferation and metastasis of hepatocellular carcinoma (HCC) cells, and acted as a tumor suppressor in HCC cells, but it had no significant effect on cell cycle. Further research found that PPP2R5A exerted tumor suppressor efficacy by inhibiting the MAPK/AKT/WNT signaling pathway. Combined with analysis of clinical tissue samples and TCGA database, it was found that the expression of PPP2R5A in tumor tissues of Chinese HCC patients was down-regulated and significantly correlated with the progression-free survival (PFS) of HCC patients. On the contrary, PPP2R5A showed an up-regulation trend in HCC cases in TCGA database although its effect on PFS was the same with that in Chinese HCC patients. HBV infection is the main pathogenic factor of HCC in China. It was found that hepatitis B virus (HBV) infection reduced the content of PPP2R5A in cells.Conclusions: It was concluded that HBV inhibited the initiation of the protective mechanism mediated by PPP2R5A, making the occurrence and progress of HCC more "unimpeded". This conclusion will further reveal the role of PPP2R5A in HBV-induced and HBV-unrelated HCC, therefore, providing clues for the prevention and treatment of the two types of HCC, respectively.


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