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TCTP participates in hepatic metabolism by regulating gene expression involved in insulin resistance

Kun Dong1, Qiuchen Zhao2, Yaqiang Xue3

  • 1Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jie Fang Avenue, Hankou, Wuhan, Hubei 430030, China.

Gene
|October 30, 2020
PubMed

Insights

Translationally controlled tumor protein (TCTP) regulates liver cell gene expression and alternative splicing. This impacts glucose and lipid metabolism, potentially influencing insulin resistance and liver diseases like NAFLD.

Area of Science:

  • Molecular Biology
  • Cellular Metabolism
  • Gene Regulation

Background:

  • Translationally controlled tumor protein (TCTP) is a multifunctional protein with known growth-promoting and antiapoptotic roles.
  • TCTP expression is elevated in high-fat diet-induced insulin resistance, suggesting a role in metabolic dysfunction.
  • The specific function of TCTP in liver metabolism remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function and molecular mechanisms of TCTP in liver cells (HepG2).
  • To elucidate TCTP's role in regulating gene expression, alternative splicing, and metabolic pathways.
  • To explore the association of TCTP with insulin resistance and liver-related diseases.

Main Methods:

  • Utilized TCTP knockdown (shTCTP) in HepG2 cells.
  • Performed transcriptome-wide gene expression analysis to identify differentially expressed genes (DEGs).
  • Analyzed effects on key metabolic enzymes, alternative splicing, and lipid levels (triglyceride, cholesterol).

Main Results:

  • TCTP knockdown altered 287 DEGs linked to apoptosis, TNF, NF-κB, glycolysis/gluconeogenesis, insulin, FoxO, adipocytokine, and AMPK signaling pathways.
  • shTCTP downregulated phosphoenolpyruvate carboxykinase (PCK1), a key gluconeogenesis enzyme.
  • TCTP regulated alternative splicing in phospholipid and glycerophospholipid metabolism, reducing triglyceride and total cholesterol levels.

Conclusions:

  • TCTP modulates the liver cell transcriptome at both transcriptional and alternative splicing levels.
  • TCTP plays a significant role in regulating glucose and lipid metabolism.
  • TCTP's regulatory network highlights its involvement in insulin resistance and potential contribution to liver diseases such as nonalcoholic fatty liver disease (NAFLD).
Keywords:
Insulin resistanceLiver metabolismRNA-seqTCTP

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