Hepatitis B virus X protein-induced upregulation of CAT-1 stimulates proliferation and inhibits apoptosis in hepatocellular carcinoma cells

Dai, Rongjuan; Peng, Feng; Xiao, Xuewen; Gong, Xing; Jiang, Yongfang; Zhang, Min; Tian, Yi; Yun, Xu; Ma, Jing; Li, Mingming; Luo, Yue; Gong, Guozhong

doi:10.18632/oncotarget.17631

Cited by 25 publications

(16 citation statements)

References 29 publications

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“…Although research regarding the expression levels and associated functions of miRNA-122 in HCC and other liver diseases have been widely carried out (15,28), the reports are diffuse and contradictory. For example, miRNA-122 acted as a cancer suppressor gene and was downregulated in HCC tissues and cells compared with the adjacent normal tissues and normal cell lines (15,29), which was in line with the results of TCGA analysis. Conversely, the serum expression levels of miRNA-122 increased significantly in HCC patients, hepatitis C patients and other liver injury diseases compared with the healthy controls (30,31).…”

Section: Discussionsupporting

confidence: 82%

Clinical value of miRNA‑122 in the diagnosis and prognosis of various types of cancer

2019

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The present study aimed to systematically analyze the value of microRNA-122 (miRNA-122) in the diagnosis and prognosis of hepatocellular carcinoma (HCC) and other types of cancer. First, the reverse transcription-quantitative polymerase chain reaction method was used to detect the expression levels of miRNA-122 in the serum samples of patients with HCC, benign lesions and healthy volunteers. Next, miRNA-seq data of miRNA-122 from The Cancer Genome Atlas database were used to analyze the differential expression and overall survival rate associated with a variety of types of cancer. Meanwhile, the target gene prediction of miRNA-122 was performed using four different software programs. Finally, 353 significant target genes were identified for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis. Finally, it was demonstrated that the expression levels of miRNA-122 in the HCC group were increased compared with the healthy group (P<0.001), but decreased with respect to the benign group (P<0.001). In addition, the combination of the miRNA-122 and a fetoprotein may further improve the diagnostic accuracy between the HCC and healthy groups (area under the curve, 0.980; 95% confidence interval, 0.958–1.000). It was also demonstrated that miRNA-122 exhibited significantly differential expression and the overall survival rate was predicted for various other types of cancer, including colorectal cancer, renal carcinoma, cholangiocarcinoma, prostate cancer and thyroid carcinoma. Functional enrichment analysis demonstrated that the target genes of miRNA-122 may contribute to the composition of the nucleus and cytoplasm, and regulate a variety of biological processes, including cardiac muscle cell differentiation and glucose metabolic processes via protein biosynthesis, estrogen and glucagon associated signaling pathways. These results revealed that miRNA-122 may be an indispensable biomarker for the diagnosis, prognostic evaluation and targeted therapy in pan-cancer.

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Section: Discussionsupporting

confidence: 82%

Clinical value of miRNA‑122 in the diagnosis and prognosis of various types of cancer

2019

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“…The overexpression of cationic amino acid transporter 1 (CAT-1) gene can inhibit the apoptosis of hepatocytes. HBx can upregulate CAT-1 expression by downregulating miR-122 expression and, ultimately, inhibit the apoptosis of hepatocytes infected with HBV [19].…”

Section: Hbx Protein Inhibits Apoptosis Of Hepatoma Cellsmentioning

confidence: 99%

The mechanism of HBx protein to promote the initiation and progression of hepatocellular carcinoma

Zhang¹,

Wei²,

Wang³

2018

Infection International

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Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the third most common cause of death from cancer, after lung and stomach cancer. Hepatitis B virus (HBV) infection is closely related to HCC and is a major cause of HCC. HBV is a lysogenic virus of the hepadnavirus family. Its genome presents a slack, ring-like, double-chain structure, containing four open reading frames. The X region encodes the product HBV X protein (HBx), which is a multifunctional regulatory protein that plays an important role in intracellular signal transduction, viral genome replication and transcription, cell proliferation and apoptosis, cell cycle progression, protein degradation, and genetic stability of hepatocytes. This article summarizes the recent research on the mechanism of promotion of initiation and progression of HCC by HBx protein.

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“…For long-term persistence in the host cells, HBV may inhibit cell death by either activating oncogenes or disrupting signaling pathways, thereby promoting the HCC progression. HBV can also inhibit apoptosis and promote HCC development through the upregulation of some pro-growth proteins, such as cationic amino acid transporter 1 (CAT-1) [ 64 ]. In some clinical cases, the CTL response is also relatively weak in chronic HBV patients, culminating in apoptosis of a smaller proportion of infected hepatocytes [ 65 , 66 ].…”

Section: Hepatitis B Virus and Apoptosismentioning

confidence: 99%

Interference of Apoptosis by Hepatitis B Virus

Lin

Zhang

2017

Viruses

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Hepatitis B virus (HBV) causes liver diseases that have been a consistent problem for human health, leading to more than one million deaths every year worldwide. A large proportion of hepatocellular carcinoma (HCC) cases across the world are closely associated with chronic HBV infection. Apoptosis is a programmed cell death and is frequently altered in cancer development. HBV infection interferes with the apoptosis signaling to promote HCC progression and viral proliferation. The HBV-mediated alteration of apoptosis is achieved via interference with cellular signaling pathways and regulation of epigenetics. HBV X protein (HBX) plays a major role in the interference of apoptosis. There are conflicting reports on the HBV interference of apoptosis with the majority showing inhibition of and the rest reporting induction of apoptosis. In this review, we described recent studies on the mechanisms of the HBV interference with the apoptosis signaling during the virus infection and provided perspective.

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Hepatitis B virus X protein-induced upregulation of CAT-1 stimulates proliferation and inhibits apoptosis in hepatocellular carcinoma cells

Cited by 25 publications

References 29 publications

Clinical value of miRNA‑122 in the diagnosis and prognosis of various types of cancer

Clinical value of miRNA‑122 in the diagnosis and prognosis of various types of cancer

The mechanism of HBx protein to promote the initiation and progression of hepatocellular carcinoma

Interference of Apoptosis by Hepatitis B Virus

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