Androgen receptor in hepatocarcinogenesis: Recent developments and perspectives

Tian, Ye; Xie, Xu; Lin, Ye; Tan, Guang; Zhong, Wen

doi:10.3892/ol.2015.3025

Cited by 30 publications

(20 citation statements)

References 63 publications

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“…The significant change in the gene expression profile of AR not only between young normal liver cells and young liver cancer cells ( p -value < 2.46☓10 -6 ) but also between old normal liver cells and old liver cancer cells ( p -value < 6.13☓10 -7 ) implicates that the gene expression change of AR may be required for hepatocarcinogenesis. The result can be supported by the most recent study in hepatocarcinogenesis [ 91 ]. HIV-1 Infection …”

Section: Discussionsupporting

confidence: 70%

Constructing an integrated genetic and epigenetic cellular network for whole cellular mechanism using high-throughput next-generation sequencing data

Chen

2016

BMC Syst Biol

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BackgroundEpigenetics has been investigated in cancer initiation, and development, especially, since the appearance of epigenomics. Epigenetics may be defined as the mechanisms that lead to heritable changes in gene function and without affecting the sequence of genome. These mechanisms explain how individuals with the same genotype produce phenotypic differences in response to environmental stimuli. Recently, with the accumulation of high-throughput next-generation sequencing (NGS) data, a key goal of systems biology is to construct networks for different cellular levels to explore whole cellular mechanisms. At present, there is no satisfactory method to construct an integrated genetic and epigenetic cellular network (IGECN), which combines NGS omics data with gene regulatory networks (GRNs), microRNAs (miRNAs) regulatory networks, protein-protein interaction networks (PPINs), and epigenetic regulatory networks of methylation using high-throughput NGS data.ResultsWe investigated different kinds of NGS omics data to develop a systems biology method to construct an integrated cellular network based on three coupling models that describe genetic regulatory networks, protein–protein interaction networks, microRNA (miRNA) regulatory networks, and methylation regulation. The proposed method was applied to construct IGECNs of gastric cancer and the human immune response to human immunodeficiency virus (HIV) infection, to elucidate human defense response mechanisms. We successfully constructed an IGECN and validated it by using evidence from literature search. The integration of NGS omics data related to transcription regulation, protein-protein interactions, and miRNA and methylation regulation has more predictive power than independent datasets. We found that dysregulation of MIR7 contributes to the initiation and progression of inflammation-induced gastric cancer; dysregulation of MIR9 contributes to HIV-1 infection to hijack CD4+ T cells through dysfunction of the immune and hormone pathways; dysregulation of MIR139-5p, MIRLET7i, and MIR10a contributes to the HIV-1 integration/replication stage; dysregulation of MIR101, MIR141, and MIR152 contributes to the HIV-1 virus assembly and budding mechanisms; dysregulation of MIR302a contributes to not only microvesicle-mediated transfer of miRNAs but also dysfunction of NF-κB signaling pathway in hepatocarcinogenesis.ConclusionThe coupling dynamic systems of the whole IGECN can allow us to investigate genetic and epigenetic cellular mechanisms via omics data and big database mining, and are useful for further experiments in the field of systems and synthetic biology.

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Section: Discussionsupporting

confidence: 70%

Constructing an integrated genetic and epigenetic cellular network for whole cellular mechanism using high-throughput next-generation sequencing data

Chen

2016

BMC Syst Biol

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“…As there are significantly fewer patients with HBV‐related HCC in C2 compared to C1, one possible explanation for the greater reduction of HCC in the male compared to the female population in C2 is the greater impact of HBV treatment in male patients compared to female patients. It has been shown that due to differential sex hormone and androgen receptor activity, HBV replication is approximately twice as efficient in male mice, which is one reason for the sex discrepancy of HBV‐related HCC 41. We postulate that the advent of highly effective nucleotide/nucleoside analogue therapy for HBV in C2 has resulted in better viremic control of HBV overall and consequently reduced HBV‐related hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 95%

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

Goh

Chang

et al. 2017

Hepatology Communications

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Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers globally. With advances in therapy for chronic viral hepatitis, changing social circumstances, and increasing practice of HCC surveillance, the epidemiology of HCC is expected to change over time. We explored the temporal trends in HCC in Singapore, a multiethnic Asian country, over the last 3 decades. Patients with HCC were prospectively enrolled and stratified into two cohorts (C1, 1988‐2002; C2, 2003‐2016). Patient and tumor characteristics, management, and survival were compared between the two cohorts, and a survival census was performed on October 31, 2015. There were 1,401 patients, and the mean age at diagnosis of HCC for C1 and C2 was 60.1 and 63.5 years, respectively. Male patient preponderance decreased significantly, with the male to female ratio falling from 5.2:1 to 3.9:1 between C1 and C2. Hepatitis B, although still the predominant risk factor for HCC, showed a significant decline from C1 to C2 (76.5% to 68.2%), while the nonviral etiology increased significantly over the same period (14.4% versus 25.0%, respectively). Significantly more patients in C2 than C1 were diagnosed through surveillance (39.2% versus 11.3%, respectively) and had better physical performance (Eastern Cooperative Oncology Group 0, 62.1% versus 20.4%, respectively). While Child‐Pugh status was comparable, significantly more patients in C2 than C1 had early stage disease (Barcelona Clinic Liver Cancer 0‐A, 39.5% versus 7.4%, respectively), which translated into significantly higher median survival (18.6 months versus 3.8 months, respectively). Conclusion: Over the past 3 decades, hepatitis B‐related HCC has been decreasing while HCC due to nonviral etiology has been increasing significantly. Surveillance to diagnose early stage HCC is important in improving the outcome of HCC. (Hepatology Communications 2017;1:564–571)

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“…Previous studies had revealed the estrogen as a protect factor in this accident [29], but the effect of androgen/AR axis seems pleiotropic [30]. In recent years, increasing evidences have considered androgen/AR axis as a motivator for tumorigenesis in prostate, liver and some other organs [31, 32], which enriched our understanding of HCC gender disparity phenomenon, but the exact mechanisms are still largely unrevealed.…”

Section: Discussionmentioning

confidence: 99%

Androgen/androgen receptor axis maintains and promotes cancer cell stemness through direct activation of Nanog transcription in hepatocellular carcinoma

et al. 2016

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Hepatocellular carcinoma (HCC) is one of the most common and malignant cancers. The HCC incidence gets a strong sexual dimorphism as men are the major sufferers in this disaster. Although several studies have uncovered the presentative correlation between the axis of androgen/androgen receptor (AR) and HCC incidence, the mechanism is still largely unknown. Cancer stem cells (CSCs) are a small subgroup of cancer cells contributing to multiple tumors malignant behaviors, which play an important role in oncogenesis of various cancers including HCC. However, whether androgen/AR axis involves in regulation of HCC cells stemness remains unclear. Our previous study had identified that the pluripotency factor Nanog is not only a stemness biomarker, but also a potent regulator of CSCs in HCC. In this study, we revealed androgen/AR axis can promote HCC cells stemness by transcriptional activation of Nanog expression through directly binding to its promoter. In HCC tissues, we found that AR expression was abnormal high and got correlation with Nanog. Then, by labeling cellular endogenous Nanog with green fluorescent protein (GFP) through CRISPR/Cas9 system, it verified the co-localization of AR and Nanog in HCC cells. With in vitro experiments, we demonstrated the axis can promote HCC cells stemness, which effect is in a Nanog-dependent manner and through activating its transcription. And the xenografted tumor experiments confirmed the axis effect on tumorigenesis facilitation in vivo. Above all, we revealed a new sight of androgen/AR axis roles in HCC and provided a potential way for suppressing the axis in HCC therapy.

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Androgen receptor in hepatocarcinogenesis: Recent developments and perspectives

Cited by 30 publications

References 63 publications

Constructing an integrated genetic and epigenetic cellular network for whole cellular mechanism using high-throughput next-generation sequencing data

Constructing an integrated genetic and epigenetic cellular network for whole cellular mechanism using high-throughput next-generation sequencing data

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

Androgen/androgen receptor axis maintains and promotes cancer cell stemness through direct activation of Nanog transcription in hepatocellular carcinoma

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