Cancers, Vol. 11, Pages 1876: HMGCS2 Mediates Ketone Production and Regulates the Proliferation and Metastasis of Hepatocellular Carcinoma

Cancers, Vol. 11, Pages 1876: HMGCS2 Mediates Ketone Production and Regulates the Proliferation and Metastasis of Hepatocellular Carcinoma Cancers doi: 10.3390/cancers11121876 Authors: Wang Liu Chiu Twu Liao Hepatocellular carcinoma (HCC) is the most common primary malignant tumor worldwide; however, the traditional therapeutic approaches and survival rates are still limited. To improve current therapies, it is necessary to investigate the molecular mechanisms underlying liver cancer and to identify potential therapeutic targets. The aims of this study were to verify the mechanisms and therapeutic potential of the ketogenesis rate-limiting enzyme 3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in HCC. Immunohistochemical staining of human liver disease tissue arrays showed that HMGCS2 is abundantly expressed in normal liver tissues but is downregulated in cirrhosis and HCC tissues. In HCC patients, lower HMGCS2 expression was correlated with higher pathological grades and clinical stages. In our investigation of the molecular mechanisms of HMGCS2 in HCC, we showed that knockdown of HMGCS2 decreased ketone production, which promoted cell proliferation, cell migration, and xenograft tumorigenesis by enhancing c-Myc/cyclinD1 and EMT signaling and by suppressing the caspase-dependent apoptosis pathway. Ketone body treatment reduced the proliferation- and migration-promoting effects of HMGCS2 knockdown in cells. In contrast, HMGCS2 overexpression increased the...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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ConclusionHaptoglobin bifucosylated tetra-antennary glycan is associated with the presence of HCC in patients with chronic liver disease including those without cirrhosis. Its combination with existing HCC biomarkers could improve the performance of standard AFP for HCC detection.
Source: Clinics and Research in Hepatology and Gastroenterology - Category: Gastroenterology Source Type: research
Early detection of liver cancer, such as hepatocellular carcinoma (HCC), is key to improve cancer-related mortality. More than 800,000 people are diagnosed with this cancer each year throughout the world. Liver cancer is also a leading cause of cancer deaths worldwide, accounting for more than 700,000 deaths each year. Currently, millions of Americans and possibly billions in the world are considered at risk for developing liver cancer. Individuals are considered at risk for developing liver cancer if they have underlying chronic liver diseases such as fibrosis and cirrhosis which in turn may be caused by viral infections ...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide with a poor prognosis. Alcoholic liver disease accounts for approximately one-third of all HCC cases. Current evidence proved that aberrant over-expression of TNFRSF12A correlates with the severity of disease, making it a likely indicator of disease a more aggressive and worse prognosis outcome. Emerging studies have confirmed that epigenetic changes are critical events in the development and progression of liver cancer. The study to investigate the mechanisms by which alcohol abuse mediated changes in the methylation level of TNFRS...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Oxidative stress is closely related to the occurrence and development of various diseases such as cancer, diabetes, and cardiovascular and infectious diseases. We identified six critical genetic variants related to oxidative stress, and evaluated their main effects and their interaction effects on hepatitis B virus (HBV)-induced liver diseases. We enrolled 3,128 Han Chinese subjects into five groups: healthy controls, chronic hepatitis B (CHB), liver cirrhosis (LC), hepatocellular carcinoma (HCC), and natural clearance. We then determined the genotypes in each group for CYBA-rs4673, NCF4-rs1883112, NOX4-rs1836882, rs301788...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
k A Abstract BACKGROUND: There is ongoing search for new noninvasive biomarkers to improve management of patients with hepatocellular carcinoma (HCC). Studies, mostly from the Asian-Pacific region, demonstrated differential expression of liver-specific microRNA-122 (miR-122) in tissue as well as in sera of patients with hepatitis B virus- and hepatitis C virus-induced HCC. AIM: To evaluate prognostic value of miR-122 in patients with HCC in a European population and determine potential factors related to alteration of miR-122 in sera. METHODS: Patients with confirmed HCC (n = 91) were included in the stu...
Source: World Journal of Gastroenterology : WJG - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
Authors: Lee YR, Park SY, Tak WY Abstract Background/Aims: The treatment outcomes and prognostic markers of acute variceal bleeding (AVB) in hepatocellular carcinoma (HCC) patients remain unclear. Therefore, we evaluated the clinical outcomes and prognostic factors of AVB in HCC patients. Methods: Cirrhotic patients with endoscopically confirmed AVB between 2007 and 2013 were enrolled in this prospective study. Prognostic factors were identified by multivariate Cox proportional hazards regression analysis. Results: Among the 329 enrolled patients, 125 patients (38.0%) were diagnosed with HCC. The 6-week mor...
Source: Gut and Liver - Category: Gastroenterology Tags: Gut Liver Source Type: research
Semin Liver Dis DOI: 10.1055/s-0039-3399534Hepatocellular carcinoma (HCC), is the most common type of liver cancer which is derived mostly from the background of chronic inflammation. Chronic hepatitis viral infection remains one of the most common etiologies implicated in chronic liver inflammation, cirrhosis, and HCC. With such background inflammation, immunotherapy—particularly the checkpoint inhibitors—have been tested in HCC patients with unprecedented success. However, despite the initial enthusiasm, the response rate to immunotherapy remains modest in most clinical trials (approximately 20%), with mixed ...
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research
This study was conducted to investigate the role of genetic variants of miR-196a2 (rs 11614913) C>T and miR-499 (rs 3746444) A>G in the development of cirrhosis and HCC in Egyptian HCV infected patients. Genotyping of the candidate SNPs was performed by Real Time PCR in 75 HCV-related HCC patients, 75 cirrhotic patients on top of HCV and 75 healthy controls. There was significant difference in miR-499 (rs3746444) genotypes frequency between the three studied groups as the GG genotype was significantly lower in HCC cases than other groups (P = 0.009) while the combined miR-499 (AA+AG) genotypes were significantly high...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
ConclusionsThe additive risk of T2DM for HCC development was highest in patients with NASH. HCC risk may vary depending on the underlying etiology.
Source: Journal of Clinical and Experimental Hepatology - Category: Gastroenterology Source Type: research
ra Grieco The biological clock controls at the molecular level several aspects of mammalian physiology, by regulating daily oscillations of crucial biological processes such as nutrient metabolism in the liver. Disruption of the circadian clock circuitry has recently been identified as an independent risk factor for cancer and classified as a potential group 2A carcinogen to humans. Hepatocellular carcinoma (HCC) is the prevailing histological type of primary liver cancer, one of the most important causes of cancer-related death worldwide. HCC onset and progression is related to B and C viral hepatitis, alcoholic an...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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