Research Progress of Bile Acids in Cancer

Fu, Junhao; Min, Yu; Xu, Wenxia; Yu, Shian

doi:10.3389/fonc.2021.778258

Cited by 29 publications

(33 citation statements)

References 108 publications

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“…Interestingly, the two different transcriptional states tS1 and tS2 of the tumor cells exhibited a distinct difference in bile acid metabolism (taurochenodeoxycholate and taurocholate synthesis and excretion), despite that each state was composed of cells from different patients with substantial transcriptional differences. The importance of bile acid metabolism is a topic of recent investigation (31), but its role in lung cancer is not clear and may be of interest for further research. The capacity of the cancer cells to synthesize heme is another interesting observation.…”

Section: Resultsmentioning

confidence: 99%

Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data

Gustafsson

Robinson

Roshanzamir

et al. 2022

Preprint

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Single-cell RNA sequencing has the potential to unravel the differences in metabolism across cell types and cell states in both the healthy and diseased human body. The use of existing knowledge in the form of genome-scale metabolic models (GEMs) holds promise to strengthen such analyses, but the combined use of these two methods requires new computational methods. Here, we present a method for generating cell-type-specific genome-scale models from clusters of single-cell RNA-Seq profiles. Specifically, we developed a method to estimate the number of cells required to pool to obtain stable models, a bootstrapping strategy for estimating statistical inference, and a faster version of the tINIT algorithm for generating context-specific GEMs. In addition, we evaluated the effect of different RNA-Seq normalization methods on model topology and differences in models generated from single-cell and bulk RNA-Seq data. We applied our methods on data from mouse cortex neurons and cells from the tumor microenvironment of lung cancer and in both cases found that almost every cell subtype had a unique metabolic profile, emphasizing the need to study them separately rather than to build models from bulk RNA-Seq data. In addition, our approach was able to detect cancer-associated metabolic differences between cancer cells and healthy cells, showcasing its utility. With the ever-increasing availability of single-cell RNA-Seq datasets and continuously improved GEMs, their combination holds promise to become an important approach in the study of human metabolism.

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Section: Resultsmentioning

confidence: 99%

Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data

Gustafsson

Robinson

Roshanzamir

et al. 2022

Preprint

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show abstract

“…Beyond its role as a digestive surfactant, bile acid has been implicated in cancer cell proliferation, metastasis, and tumor angiogenesis [ 2 ]. Elevated serum bile acid levels have been identified as a significant risk factor for gastrointestinal cancers [ 4 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Not only do bile acids (BAs) influence cholesterol metabolism via synthesis and excretion, but they have also recently been identified as signaling molecules in the tumor microenvironment [ 1 , 2 ]. The first and rate-limiting enzyme in bile acid production was cholesterol 7-hydroxylase (CYP7A1) [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Survival Benefit of Statin with Anti-Angiogenesis Efficacy in Lung Cancer-Associated Pleural Fluid through FXR Modulation

Tsai

Changchien

Chen

et al. 2022

Cancers

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Lung cancer-related pleural fluid (LCPF) presents as a common complication with limited treatment. Beyond its function in lipid digestion, bile acid was identified as a potent carcinogen to stimulate tumor proliferation. Previous research indicated a correlation between serum bile acid levels and the risk of developing several gastrointestinal cancers. Our study identified elevated bile acid levels in LCPF and increased farnesoid X receptor (FXR) expression as bile acid nuclear receptors in pleural microvessels of lung adenocarcinoma. Additionally, LCPF stimulated the expression of proteins involved in bile acid synthesis and cholesterol metabolism in HUVECs including CYP7A1, StAR, HMGCR, and SREBP2. LCPF-induced endothelial motility and angiogenesis were counteracted by using β-muricholic acid as an FXR antagonist. Moreover, we investigated the efficacy of cholesterol-lowering medications, such as cholestyramine, fenofibrate, and atorvastatin, in regulating LCPF-regulated angiogenesis. Along with suppressing endothelial proliferation and angiogenesis, atorvastatin treatment reversed cholesterol accumulation and endothelial junction disruption caused by LCPF. Statin treatment inhibited LCPF-induced endothelial FXR expression as well as the downstream proteins RXR and SHP. Based on the positive findings of suppressing endothelial angiogenesis, our group further incorporated the effect of statin on clinical patients complicated with LCPF. A Kaplan–Meier analysis revealed the clinical benefit of statin exposure in patients with lung adenocarcinoma with LCPF. Conclusively, our study demonstrated the ability of statin to alleviate LCPF-induced angiogenesis in patients with LCPF via FXR modulation.

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“…The hydrophobicity of bile acids (in the order of LCA > DCA > CDCA > CA > UDCA) is closely related to the number and position of the hydroxyl groups attached to bile acids, and is a fundamental factor determining their biological activity [67]. However, the cytotoxicity of bile acids at the level of apoptosis induction does not always correlate with hydrophobicity.…”

Section: Bile Acid-related Apoptosismentioning

confidence: 99%

“…27-Hydroxycholesterol is continuously converted to CDCA instead of CA, with the participation of oxysterol 7α hydroxylase (CYP7B1). The alternative pathway is the secondary pathway of bile acid synthesis, which accounts for approximately 10% of bile acid production, and is generally considered active in pathological conditions [67,96,97]. After primary bile acid synthesis, taurine or glycine is conjugated to a 1:3 ratio via covalent modifications (known as bile salts) that improve solubility while reducing toxicity [98].…”

Section: Effects Of Primary Bile Acids On Apoptosismentioning

confidence: 99%

Mechanism of Bile Acid-Induced Programmed Cell Death and Drug Discovery against Cancer: A Review

Jang

Choi

Kim

2022

IJMS

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Bile acids are major signaling molecules that play a significant role as emulsifiers in the digestion and absorption of dietary lipids. Bile acids are amphiphilic molecules produced by the reaction of enzymes with cholesterol as a substrate, and they are the primary metabolites of cholesterol in the body. Bile acids were initially considered as tumor promoters, but many studies have deemed them to be tumor suppressors. The tumor-suppressive effect of bile acids is associated with programmed cell death. Moreover, based on this fact, several synthetic bile acid derivatives have also been used to induce programmed cell death in several types of human cancers. This review comprehensively summarizes the literature related to bile acid-induced programmed cell death, such as apoptosis, autophagy, and necroptosis, and the status of drug development using synthetic bile acid derivatives against human cancers. We hope that this review will provide a reference for the future research and development of drugs against cancer.

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Research Progress of Bile Acids in Cancer

Cited by 29 publications

References 108 publications

Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data

Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data

Survival Benefit of Statin with Anti-Angiogenesis Efficacy in Lung Cancer-Associated Pleural Fluid through FXR Modulation

Mechanism of Bile Acid-Induced Programmed Cell Death and Drug Discovery against Cancer: A Review

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