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In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
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Related Experiment Video

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Network analyses identify liver-specific targets for treating liver diseases.

Sunjae Lee1, Cheng Zhang1, Zhengtao Liu1

  • 1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden.

Molecular Systems Biology
|August 23, 2017
PubMed
Summary

Researchers identified novel liver-specific genes, including PKLR, PNPLA3, and PCSK9, that are potential therapeutic targets for treating nonalcoholic fatty liver disease (NAFLD) and liver cancer (HCC) with minimal side effects.

Keywords:
HCCNAFLDco‐expressionco‐regulationmetabolism

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Area of Science:

  • Genomics
  • Molecular Biology
  • Hepatology

Background:

  • Nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are characterized by increased *de novo* lipogenesis.
  • Identifying specific molecular targets is crucial for developing effective treatments with minimal side effects.

Purpose of the Study:

  • To identify liver-specific genes co-expressed with fatty acid synthase (FASN) using integrative network analyses.
  • To validate the functional roles of these genes in liver fat accumulation and cell growth.
  • To explore potential therapeutic targets for NAFLD and HCC.

Main Methods:

  • Generated co-expression networks (CNs) across 46 human tissues and liver cancer.
  • Examined overlap between functional and physical gene interactions.
  • Performed experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes.

Main Results:

  • CN analyses predicted that inhibiting specific liver genes decreases FASN expression.
  • Experimental validation confirmed functional relationships between identified liver genes.
  • Inhibition of these genes reduced cell growth and liver fat content in experimental models.

Conclusions:

  • Identified liver-specific genes, including pyruvate kinase liver and red blood cell (PKLR), patatin-like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), are linked to NAFLD and HCC pathogenesis.
  • These genes represent promising targets for novel drug development for liver diseases.