scholarly journals Involvement of TRPC7-AS1 Expression in Hepatitis B Virus-Related Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Shaoliang Zhu ◽  
Hang Ye ◽  
Xiaojie Xu ◽  
Weiru Huang ◽  
Ziyu Peng ◽  
...  

Objective. To investigate the expression of transient receptor potential (TRP) superfamily genes, especially TRPC7-AS1 in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). Methods. Three cancer samples of HBV-related HCC at phase IV and matched paracancerous liver tissues were included in the study. Total RNA was extracted, and differential expression of RNA was screened by high-throughput transcriptome sequencing. The expression of TRPC7-AS1 was detected by quantitative real-time PCR. The N6-adenosyl methylation RNA in MHCC97H, HepG2, and HL-7702 was enriched by coimmunoprecipitation with m6A antibody, and the relative level of N6-adenosyl methylation RNA in TRPC7-AS1 was detected. Results. The expression of TRP family genes in cancer tissues was higher than that in paracancerous liver tissues, including TRPC7-AS1, TRPC4AP, PKD1P6, and PKD1P1. Moreover, the expression level of TRPC7-AS1 in MHCC97H and HepG2 was also significantly higher than that in L02, a normal liver cell. The methylation level of N6-adenosine of TRPC7-AS1 was lower in HepG2 cells than that in L02 cells. Conclusion. TRP superfamily genes, especially TRPC7-AS1, were highly expressed in HBV-related HCC. TRPC7-AS1 could be a potential therapeutic target or diagnostic marker for HCC.

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Fugui Bai ◽  
Yoshihiko Yano ◽  
Takumi Fukumoto ◽  
Atsushi Takebe ◽  
Motofumi Tanaka ◽  
...  

Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P<0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.


2021 ◽  
Author(s):  
Rui Pu ◽  
Wenbin Liu ◽  
Xinyu Zhou ◽  
Xiaomei Hou ◽  
Shiliang Cai ◽  
...  

Abstract Background: We aimed to elucidate the mechanism by which hepatitis B virus X (HBx) gene mutations increase the risk of hepatocellular carcinoma (HCC) and identify novel therapeutic targets.Methods: Wild-type and four HBx mutants (M1, A1762T/G1764A; M2, T1674G+T1753C+A1762T/G1764A; M3, C1653T+T1674G+A1762T/G1764A; Ct-HBx, carboxylic acid-terminal truncated HBx) were delivered into the livers of fumarylacetoacetate hydrolase-deficient mice by using the Sleeping Beauty (SB) transposon system, respectively. Seven liver tissues and seven tumor tissues of the SB mouse models were subjected to HBV-capture sequencing. Three liver tissues from WT-HBx mice, three tumor tissues from M3-HBx mice, and three tumor tissues from Ct-HBx mice were subjected to cDNA microarray analysis. HeLa cells stably expressing WT-HBx and the four HBx mutants were also subjected to cDNA microarray assay.Results: The incidence of HCC was higher in the mice injected with M3-HBx or Ct-HBx. M3-HBx had a stronger capacity of upregulating inflammatory cytokines than other HBx variants. HBV-capture sequencing showed that the HBx fragments were mainly integrated into intergenic and intron regions. No significant difference was observed in the number of insertion sites between tumors and liver tissues. Ectopic expression of the HBx mutants, especially M3-HBx and Ct-HBx, significantly increased cell proliferation and the S phase proportion of HepG2 and HeLa cells, compared to WT-HBx. Liver tissues of the SB mice and the transfected cells were subjected to cDNA microarray analysis. Plasminogen activator inhibitor-1 (PAI1) and cell division cycle 20 (CDC20) were identified as novel effectors. M3-HBx and Ct-HBx significantly upregulated the expression of PAI1 and CDC20 in HepG2 and HeLa cells as well as the livers of the SB mice. PAI1 silencing attenuated the effect of M3-HBx and Ct-HBx on the growth of HepG2 cells and greatly decreased the growth of HeLa cells with Ct-HBx. Conclusion: HBx C1653T+T1674G+A1762T/G1764A mutant and Ct-HBx promote carcinogenesis via upregulating PAI1 and CDC20. PAI1, an important player bridging the HBx mutants and HCC, should be a promising candidate as a predictive and prognostic biomarker and therapeutic target in HBV-related HCC.


1988 ◽  
Vol 25 (3) ◽  
pp. 249-258 ◽  
Author(s):  
Ming-Yang Lai ◽  
Ding-Shinn Chen ◽  
Pei-Jer Chen ◽  
Sheng-Chung Lee ◽  
Jin-Chuan Sheu ◽  
...  

2019 ◽  
pp. 113-123 ◽  
Author(s):  
Zhiyuan WEI ◽  
Xiaohe SHEN ◽  
Bing NI ◽  
Gaoxing LUO ◽  
Yi TIAN ◽  
...  

The hepatitis B virus-encoded X (HBX) protein plays important roles in Hepatocellular carcinoma (HCC). Previous studies have demonstrated that HBX can induce alterations in the expression of numerous microRNAs (miRNAs) involved in the carcinogenesis of various tumors. However, the global profile of liver miRNA changes induced by HBX has not been characterized. In this study, we conducted a miRNA microarray analysis to investigate the influence of HBX on the expression of total miRNAs in liver in relation to HCC. Comparative analysis of the data from human normal liver cells (L02) and human HCC cells (HepG2), with or without HBX, identified 19 differentially expressed miRNAs, including 5 with known association to HBX. Target gene prediction for the aberrantly expressed miRNAs identified a total of 304 potential target genes, involved in sundry pathways. Finally, pathway analysis of the HBXinduced miRNAs pathway showed that 5 of the total miRNAs formed an internetwork, suggesting that HBX might exert its pathological effects on hepatic cells through functional synergy with miRNAs that regulated common pathways in liver cells. Therefore, this work provides new insights into the mechanisms of HCC as well as potential diagnostic markers or therapeutic targets for use in clinical management of HCC.


Author(s):  
Ying Li ◽  
Chaomin Wang ◽  
Ting Zhao ◽  
Ranliang Cui ◽  
Linfei Hu ◽  
...  

Background: Hepatitis B virus X protein (HBx) is an indispensable progression factor in hepatocellular carcinoma (HCC). CCL15 could be a peculiar proteomic biomarker of HCC with tumorigenesis and tumor invasion. Objective: The aim of study was to explore the relationship between HBx and CCL15 expression in HCC. Methods: HBV–positive HCC pathological tissue samples and corresponding adjacent non-tumor liver tissues were clearly collected. The expression of HBx and CCL15 was analyzed by immunohistochemistry, real-time polymerase chain reaction (PCR) and western blot analysis in tissues or in vitro. Results: The levels of CCL15 mRNA and protein expression in HCC samples were observably higher than the ones of adjacent non-tumor liver tissues. The CCL15 was significantly associated with the expression of HBx in HBV-positive HCC samples. The up-regulation of HBx induced CCL15 expression in vitro. The high expression score of CCL15 was significant associated with the poor prognosis of HCC patients. Conclusions: The CCL15 expression was observably associated with HBx in HCC patients. The CCL15 may be considered as a indicator in clinical managment of HBV-associated HCC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanyuan Ren ◽  
Lei Yang ◽  
Man Li ◽  
Jian Wang ◽  
Huimin Yan ◽  
...  

AbstractHBV infection is recognized as a serious global health problem, and hepatitis B virus infection is a complicated chronic disease leading to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). New biochemical serum markers could be used to advance the diagnosis and prognosis of HBV-associated liver diseases during the progression of chronic hepatitis B into cirrhosis and HCC. We determined whether the 4210 Da and 1866 Da polypeptides are serum metabolite biomarkers of hepatopathy with hepatitis B virus. A total of 570 subjects were divided into five groups: healthy controls, those with natural clearance, and patients with CHB, LC, and HCC. The 1866 Da and 4210 Da polypeptides were measured by Clin-ToF II MALDI-TOF–MS. There were significant differences in 4210 Da and 1866 Da levels among the five groups (P < 0.001). For the differential diagnosis of CHB from normal liver, the areas under the receiver operating characteristic (ROC) curve of 4210 Da and 1866 Da and their combination via logistic regression were 0.961, 0.849 and 0.967. For the differential diagnosis of LC from CHB, the areas under the ROC curve were 0.695, 0.841 and 0.826. For the differential diagnosis of HCC from CHB, the areas under the ROC curve were 0.744, 0.710 and 0.761, respectively. For the differential diagnosis of HCC from LC, the areas under the ROC curve of 4210 Da and 1866 Da were 0.580 and 0.654. The positive rate of 1866 Da was 45.5% and 69.0% in AFP-negative HCC patients and that of 4210 Da was 60.6% 58.6% in AFP-negative HCC patients of the study HCC vs. CHB and HCC vs. LC. The 4210 Da and 1866 Da polypeptide levels were positively correlated with HBV DNA levels (P < 0.001, r = 0.269; P < 0.001, r = 0.285). The 4210 Da and 1866 Da polypeptides had good diagnostic value for the occurrence and progression of HBV-related chronic hepatitis, liver cirrhosis and hepatocellular carcinoma and could serve to accurately guide treatment management and predict clinical outcomes.


Virology ◽  
1992 ◽  
Vol 188 (2) ◽  
pp. 890-895 ◽  
Author(s):  
Aldo Manzin ◽  
Stefano Menzo ◽  
Patrizia Bagnarelli ◽  
Pietro E. Varaldo ◽  
Italo Bearzi ◽  
...  

2021 ◽  
Vol 18 ◽  
pp. 100077
Author(s):  
Doha El-Sayed Ellakwa ◽  
Mohamed Abdel-Hamid ◽  
Mohamed Seif EL-Din Ashour ◽  
Laila El- Sayed Khairy ◽  
Ola Sayed M. Ali

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