Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells

Bort, Alicia; Miguel, Irene de; Mateos-Gómez, Pedro A.; Díaz‐Laviada, Inés

doi:10.1007/s11033-020-05352-3

Cited by 31 publications

(27 citation statements)

References 52 publications

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“…Furthermore, the protein expressions of ACC and ACLY were decreased in our study and this may be explained by the following reasons. First, inhibition of FASN can decrease the expressions of other de novo lipogenic enzymes, such as ACC and ACLY (Bort & Sanchez, 2020; Lee & Zhang, 2017; Sadowski et al, 2014). Second, like m 6 A‐mediated FASN mRNA degradation, ACC and ACLY mRNA levels might be declined due to the increased m 6 A levels caused by FTO knockdown.…”

Section: Discussionmentioning

confidence: 99%

Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Sun

Zhao

Zhang

et al. 2020

Cell Biology International

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As the first identified N6‐methyladenosine (m6A) demethylase, fat mass and obesity‐associated (FTO) protein is associated with fatty acid synthase (FASN) and lipid accumulation. However, little is known about the regulatory role of FTO in the expression of FASN and de novo lipogenesis through m6A modification. In this study, we used FTO small interfering RNA to explore the effects of FTO knockdown on hepatic lipogenesis and its underlying epigenetic mechanism in HepG2 cells. We found that knockdown of FTO increased m6A levels in total RNA and enhanced the expression of YTH domain family member 2 which serves as the m6A‐binding protein. The de novo lipogenic enzymes and intracellular lipid content were significantly decreased under FTO knockdown. Mechanistically, knockdown of FTO dramatically enhanced m6A levels in FASN messenger RNA (mRNA), leading to the reduced expression of FASN mRNA through m6A‐mediated mRNA decay. The protein expressions of FASN along with acetyl CoA carboxylase and ATP‐citrate lyase were further decreased, which inhibited de novo lipogenesis, thereby resulting in the deficiency of lipid accumulation in HepG2 cells and the induction of cellular apoptosis. The results reveal that FTO regulates hepatic lipogenesis via FTO‐dependent m6A demethylation in FASN mRNA and indicate the critical role of FTO‐mediated lipid metabolism in the survival of HepG2 cells. This study provides novel insights into a unique RNA epigenetic mechanism by which FTO mediates hepatic lipid accumulation through m6A modification and indicates that FTO could be a potential target for obesity‐related diseases and cancer.

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Section: Discussionmentioning

confidence: 99%

Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Sun

Zhao

Zhang

et al. 2020

Cell Biology International

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“…Approximately 93% of the fatty acids in tumor cells are synthesized de novo (69,70). The enzymes involved in the fatty acid synthesis, such as ATP citrate lyase (ACLY), Acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN) are changed in tumor cells (71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83). Citrate, the intermediate product of glucose metabolism, forms Ac-CoA under the catalysis of ACLY, and Ac-CoA forms malonyl CoA (Mal-CoA) under the catalysis of ACC.…”

Section: Enhancement Of De Novo Lipid Synthesismentioning

confidence: 99%

Metabolic Reprogramming of Thyroid Cancer Cells and Crosstalk in Their Microenvironment

Bao

et al. 2021

Front. Oncol.

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Metabolism differs significantly between tumor and normal cells. Metabolic reprogramming in cancer cells and metabolic interplay in the tumor microenvironment (TME) are important for tumor formation and progression. Tumor cells show changes in both catabolism and anabolism. Altered aerobic glycolysis, known as the Warburg effect, is a well-recognized characteristic of tumor cell energy metabolism. Compared with normal cells, tumor cells consume more glucose and glutamine. The enhanced anabolism in tumor cells includes de novo lipid synthesis as well as protein and nucleic acid synthesis. Although these forms of energy supply are uneconomical, they are required for the functioning of cancer cells, including those in thyroid cancer (TC). Increasing attention has recently focused on alterations of the TME. Understanding the metabolic changes governing the intricate relationship between TC cells and the TME may provide novel ideas for the treatment of TC.

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“…Lipid metabolism assays showed that compared with normal cells, cancer cells increased the expression of ATP-citrate lyase, acetyl coenzyme A (acetyl-CoA) carboxylase, and fatty acid (FA) synthase that is involved in de novo lipid synthesis (Bort et al. 2020 ). Lipid metabolism mainly includes de novo fatty acid synthesis, the triglyceride synthesis pathway, and fatty acid β-oxidation, which subsequently affect the proliferation, metabolism, and metastasis of cancer cells (as shown in Figure 2 ) (Vander Heiden et al.…”

Section: Abnormal Glucose Metabolism and Lipid Metabolismmentioning

confidence: 99%

Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors

Zeng

Zhu

et al. 2021

Drug Delivery

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Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells

Cited by 31 publications

References 52 publications

Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Metabolic Reprogramming of Thyroid Cancer Cells and Crosstalk in Their Microenvironment

Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors

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Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells

Cited by 31 publications

References 52 publications

Fat mass and obesity‐associated protein regulates lipogenesis via m6A modification in fatty acid synthase mRNA

Fat mass and obesity‐associated protein regulates lipogenesis via m6A modification in fatty acid synthase mRNA

Metabolic Reprogramming of Thyroid Cancer Cells and Crosstalk in Their Microenvironment

Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors

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Product

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Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA