Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SIRT5 loss promotes hepatocarcinogenesis via bile acid-induced immunosuppressive microenvironment

ABSTRACT: SIRT5 loss promotes hepatocarcinogenesis via bile acid-induced immunosuppressive microenvironment

PROVIDER: PRJNA795446 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

SIRT5 loss promotes hepatocarcinogenesis via bile acid-induced immunosuppressive microenvironment

Project description:Hepatocellular carcinoma (HCC) is a prototypical inflammation-associated cancer and the tumor microenvironment (TME) plays a pivotal role in HCC pathogenesis and response to therapy. The liver is a metabolically active organ, but how liver metabolism impacts TME during HCC development and response to immunotherapy are poorly understood. Here, we show that the metabolic regulator SIRT5 is downregulated in human primary HCC samples, and that Sirt5 deficiency in mice synergizes with oncogenes to increase bile acid (BA) production, which is due to hypersuccinylation and increased BA biosynthesis in the peroxisome. BA acts as a cell-signaling mediator to stimulate its nuclear receptor and promotes M2-like macrophage polarization, thereby creating an immunosuppressive microenvironment favorable for HCC initiating cells. Furthermore, high serum taurocholic acid, a major primary BA, correlates with low SIRT5 expression and increased M2-like tumor-associated macrophages (TAMs) in liver tissue samples from HCC patients. Importantly, administration of cholestyramine, a BA sequestrant and FDA-approved medication for hyperlipemia, reverses the effect of Sirt5 deficiency on promoting M2-like polarized TAMs and liver tumor growth. Our study thus uncovers a novel function of SIRT5 in orchestrating BA metabolism to prevent tumor immune evasion and suppress HCC. These results also suggest a potential strategy using clinically proven bile acid sequestrants for the treatment of HCC patients, especially those with decreased SIRT5 and abnormally high BAs.

2022-01-10 | GSE193213 | GEO

TERT activates endogenous retroviruses to promote an immunosuppressive tumour microenvironment

Project description:TERT activates endogenous retroviruses to promote an immunosuppressive tumour microenvironment

| PRJNA717744 | ENA

TERT activates endogenous retroviruses contributing to immunosuppressive tumour microenvironment I

Project description:TERT activates endogenous retroviruses contributing to immunosuppressive tumour microenvironment I

| PRJNA717750 | ENA

TERT activates endogenous retroviruses contributing to immunosuppressive tumour microenvironment III

Project description:TERT activates endogenous retroviruses contributing to immunosuppressive tumour microenvironment III

| PRJNA717753 | ENA

TERT activates endogenous retroviruses contributing to immunosuppressive tumour microenvironment II

Project description:TERT activates endogenous retroviruses contributing to immunosuppressive tumour microenvironment II

| PRJNA717754 | ENA

Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment

Project description:Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment

| PRJNA601726 | ENA

Lysyl Oxidase-Like 4 Fosters an Immunosuppressive Microenvironment During Hepatocarcinogenesis.

Project description: Not available

| S-EPMC8251926 | biostudies-literature

Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis

Project description:Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a pathophysiological pathway very similar to that observed in obese humans. This process initiates with non-alcoholic fatty liver disease (NAFLD), progresses to steatohepatitis and fibrosis before HCC detection, and is driven by persistent genome-wide gene deregulation that induces global liver metabolic dysfunction. Nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism are found among top deregulated pathways. Ablation of the bile acid receptor FXR dramatically increases intrahepatic bile acid levels and jet-lag-induced HCC, while loss of CAR, a well-known liver tumor promoter, inhibits NAFLD-induced hepatocarcinogenesis. Circadian disruption activates CAR by promoting cholestasis, peripheral clock disruption, and sympathetic dysfunction. Thus, FXR and CAR are clock-controlled therapeutic targets for spontaneous HCC

2016-11-23 | GSE75475 | GEO

Tumor-infiltrating Monocytic Myeloid-derived suppressor cells play a key role in forming immunosuppressive microenvironment in human gastric cancer

Project description:The present data suggest that M-MDSC, play a predominant role in forming the immunosuppressive microenvironment in GC.

2024-01-22 | GSE231539 | GEO

Bile acid therapeutics for NASH

Project description:Bile acid therapeutics for NASH

| PRJNA705980 | ENA