HCC and androgen receptor

BACKGROUND: Hepatocellular carcinoma (HCC) ranks many tasks in clinical oncology due to possibly develop general tumor in men and, usually lead to malignant to death within years. Researches had reported about major factors for being HCC was male sex and HCC associated with cirrhosis in childhood was found more common in males than females. In certain mouse strains as studied, breeding with testosterone significantly increases the development of HCC. Furthermore, castration of male mice diminished the frequency of the development of liver tumors...

Androgen receptor (AR) has been reported to play an important role in the development and progression of man's prostate cancer. Hepatocellular carcinoma (HCC) is also male-dominant, but the role of AR in HCC remains poorly understood. Here we show that mTORC1 interacts with hepatic AR and phosphorylates it at S96 in response to nutrient and mitogenic stimuli in HCC cells. S96 phosphorylation promotes the stability, nuclear localization and transcriptional activity of AR, which enhances de novo lipogenesis and proliferation in hepatocytes and induces liver steatosis and hepatocarcinogenesis in mice independently and cooperatively with androgen...

BACKGROUND & AIMS: Contradictory roles of the androgen receptor (AR) in hepatocellular carcinoma (HCC) metastasis have been reported. We have shown that VETC (vessels encapsulating tumor clusters) mediates invasion-independent metastasis, whereas VETC- HCCs metastasize in an invasion-dependent manner. Here we aimed to reveal the roles of AR in HCC metastasis. METHODS: Mouse xenograft models, clinical samples, and cell models were used. RESULTS: AR expression was significantly lower in HCCs with VETC pattern, portal vein tumor thrombus, endothelium-coated microemboli or high recurrence rates...

Development of novel targeted therapies remains the priority in hepatocellular carcinoma (HCC) treatments. Early reports have demonstrated that androgen receptor (AR) plays a suppressive role in HCC progression. However, the underlying mechanisms by which AR attenuates HCC development are still elusive, especially under hypoxic conditions. Herein, we demonstrated that AR/circ-LNPEP/miR-532-3p/RAB9A signaling axis was tightly involved in hypoxia-induced cell invasion of HCC cells. AR worked as a transcription factor to reduce circ-LNPEP expression level, which released its sponge potential of miR-532-3p, leading to the downregulation of RAB9A and inhibiting cell invasion of HCC cells...

Hepatocellular carcinoma (HCC) is the most 5th commonly diagnosed and 2nd most lethal tumor in the world. The obvious gender advantage of HCC indicates that androgen receptor (AR) may play an important role in the tumor occurrence, develop and metastasis of HCC. Here we found that decreased AR could alter miR-325 to increase ACP5 expression in HCC cells, to increase HCC cells migration and invasion capacities. Mechanism dissection revealed that AR could regulate miR-325 expression through transcriptional regulation and miR-325 might directly target the 3'UTR of ACP5-mRNA to suppress its translation...

A promotional role for androgen receptor (AR) signaling in hepatocellular carcinogenesis is emerging. In pre-clinical models, including diethylnitrosamine- (DEN-) induced hepatocellular carcinoma (HCC), anti-androgen therapies delay hepatocarcinogenesis. However, pharmacologic anti-androgen therapy in advanced HCC patients fails, suggesting that AR plays a role in HCC onset. This study aims to characterize AR expression and function throughout DEN-induced liver inflammation and carcinogenesis and evaluate the efficacy of prophylactic AR antagonism to prevent hepatocarcinogenesis...

Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and a leading cause of cancer deaths worldwide. HCC is a male-dominant cancer with a male:female ratio of up to 7:1. The androgen receptor (AR) is the male hormone receptor known as a major oncogenic driver of prostate cancer. Although AR has been linked to the sexual dimorphism of HCC, clinical trials with AR-targeted agents failed to generate survival benefits. Recent studies provide new insights into the role of AR in liver tumorigenesis and therapeutic responses...

Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer and the majority of patients are diagnosed at an advanced stage and have a poor prognosis. AKR1C3 (Aldo-keto reductase family 1 member C3) and AKR1D1 (Aldo-keto reductase family 1 member D1) catalyze the conversion of aldehydes and ketones to alcohols and play crucial roles in multiple cancers. However, the functions of AKR1C3 and AKR1D1 in HCC remain unclear. In our study, data from the public databases were selected as training and validation sets, then 76 HCC patients in our center were chosen as a test set...

The role of the Androgen Receptor (AR) expression and its activity in the prognosis of hepatocellular carcinoma (HCC) remains inconclusive. The aim of this study is to analyze the role of the AR expression and its activity as prognostic biomarkers in HCC. Three-hundred and thirty-seven patients from The Cancer Genome Atlas (TCGA) (107 females; 59.42 years [SD = 13.0]) were included. To infer AR activity, the expression-profile of previously validated androgen responsive genes (ARGs) was included. AR activity was shown by the AR-Score-21 (21 ARGs) and AR-Score-13 (13 ARGs) that were computed based on the expression of the selected ARGs...

Androgen receptor (AR) can suppress hepatocellular carcinoma (HCC) invasion and metastasis at an advanced stage. Vasculogenic mimicry (VM), a new vascularization pattern by which tumour tissues nourish themselves, is correlated with tumour progression and metastasis. Here, we investigated the effect of AR on the formation of VM and its mechanism in HCC. The results suggested that AR could down-regulate circular RNA (circRNA) 7, up-regulate micro RNA (miRNA) 7-5p, and suppress the formation of VM in HCC Small hairpin circR7 (ShcircR7) could reverse the impact on VM and expression of VE-cadherin and Notch4 increased by small interfering AR (shAR) in HCC, while inhibition of miR-7-5p blocked the formation of VM and expression of VE-cadherin and Notch4 decreased by AR overexpression (oeAR) in HCC...

Introduction: Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers and is ranked as the fifth most common malignancy. Androgen receptor (AR) may promote the progression of HCC at an early stage of the disease. However, this study identified miR-135b-5p as an AR upstream regulator can suppress AR protein expression and inhibit HCC proliferation, consistent with the idea that AR expression is negatively correlated with HCC progression. Methods: The target microRNAs were predicted using online databases (TargetScan, miRDB, and MicroCosm Targets)...

Androgen receptor (AR) signaling is considered to be crucial for the pathogenesis of hepatocellular carcinoma (HCC) with obvious sexual dimorphism. Pre-mRNA processing factor 6 (PRPF6) was identified as a coactivator of AR. However, what is the molecular mechanism underlying the modulation function of PRPF6 on AR-mediated transcriptional activity in HCC needs to be further clarified. In this study, we analyzed the data from TCGA to show that PRPF6 is highly expressed in HCC. The highly expression of PRPF6 is positively correlated with the poor prognosis...

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PURPOSE: Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), which has a male predominance, lacks effective therapeutic options. Previously, the cardiac glycoside analogue bufalin has been found to inhibit HBV infection and HCC development. As yet, however, its molecular role in HBV-associated HCC has remained obscure. METHODS: Colony formation and soft agar assays, xenograft and orthotopic mouse models and HBV X protein (HBx) transgenic mice with exposure to diethylnitrosamine were used to evaluate the effect of bufalin on HBV-associated HCC growth and tumorigenicity...

Early studies indicated that the androgen receptor (AR) might play important roles in the regulating of the initiation and progression of hepatocellular carcinoma (HCC), but its linkage to the surrounding macrophages and their impacts on the HCC progression remain unclear. Here we found that macrophages in liver cancer might function via altering the microRNA, miR-92a-2-5p, in exosomes to decrease liver cancer cells AR expression, which might then lead to increase the liver cancer cells invasion. Mechanism dissection revealed that miR-92a-2-5p from the exosomes could target the 3'UTR of AR mRNA to suppress AR translation, altering the PHLPP/p-AKT/β-catenin signaling to increase liver cancer cells invasion...

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with gender-related differences in onset and course. Androgen receptor (AR), a male hormone receptor, is critical in the initiation and progression of HCC. The role of AR in HCC has been mechanistically characterized and anti-AR therapies have been developed, showing limited efficacy. Immunotherapy targeting immune checkpoint proteins may substantially improve the clinical management of HCC. The mechanism by which AR influences HCC immune state remains unclear...

LESSONS LEARNED: Androgen receptor as assessed by immunohistochemistry is expressed in a high proportion of patients with hepatocellular carcinoma (HCC). Enzalutamide at 160 mg orally daily is safe and tolerable in patients with advanced HCC but has no single-agent antitumor activity. Enzalutamide, a CYP3A4 inducer, at a standard dose of 160 mg reduces the exposure of sorafenib, a CYP3A4 substrate. Enzalutamide and sorafenib is safe and tolerable in patients with advanced HCC, but the addition of enzalutamide to sorafenib did not enhance the antitumor activity of sorafenib...

Emodin is a promising anti-cancer reagent. To improve the physicochemical and anti-cancer property, we modified its structure and get a derivative called emodin succinyl ester (ESE). Here, we investigated the effect of ESE on the suppression of hepatocellular carcinoma (HCC) and the underlying mechanism. Our results showed that ESE strongly inhibited HCC cell proliferation and migration in vitro. Further study revealed that ESE treatment decreased transcription level and protein expression of androgen receptor (AR) and enhancer of zeste homolog 2 (EZH2), two key factors interacting to promote aggressive HCC development...

Sexual dimorphism is associated not only with somatic and behavioral differences between men and women, but also with physiological differences reflected in organ metabolism. Genes regulated by sex hormones differ in expression in various tissues, which is especially important in the case of liver metabolism, with the liver being a target organ for sex hormones as its cells express estrogen receptors (ERs: ERα, also known as ESR1 or NR3A; ERβ; GPER (G protein-coupled ER, also known as GPR 30)) and the androgen receptor (AR) in both men and women...

BACKGROUND: Hepatocellular carcinoma (HCC) escapes growth inhibition by upregulating hexokinase 2 (HK2); however, the mechanism by which tumor cells upregulate HK2 remains unclear. AIM: We aimed to investigate the role of androgen receptor (AR) signalling in promoting HK2 expression in HCC. METHODS: The expressions of AR and HK2 in HCC tissues were analyzed by immunohistochemistry. Cell proliferation was determined using the CCK-8 assay, and the molecular mechanism of AR in the regulation of HK2 was evaluated by immunoblotting and luciferase assays...