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Related Experiment Video

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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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LncRNA FRMD6-AS1/miR-491-5p/USP13 pathway attenuated ferroptosis and contributed to liver fibrosis.

Ziqiang Li1, Weilong Zou1, Xiangren Jin1

  • 1Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Environmental Toxicology
|April 1, 2024
PubMed
Summary
This summary is machine-generated.

Long non-coding RNA FRMD6-AS1 promotes liver fibrosis by inhibiting ferroptosis in hepatic stellate cells (HSCs). Knocking down FRMD6-AS1 alleviates liver fibrosis by regulating the miR-491-5p/USP13 pathway.

Keywords:
LncRNA FRMD6‐AS1USP13ferroptosisliver fibrosismiR‐491‐5p

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Area of Science:

  • Hepatology
  • Molecular Biology
  • Biochemistry

Background:

  • Liver fibrosis involves excessive extracellular matrix (ECM) accumulation and hepatic stellate cell (HSC) activation.
  • Inducing ferroptosis in HSCs can mitigate liver fibrosis.
  • Long non-coding RNAs (lncRNAs) influence ferroptosis and ECM deposition in liver fibrosis.

Purpose of the Study:

  • To investigate the role of lncRNA FRMD6-AS1 in liver fibrosis.
  • To elucidate the underlying molecular mechanisms involving ferroptosis and HSC activation.

Main Methods:

  • Assessed FRMD6-AS1 expression in activated HSCs.
  • Performed knockdown of FRMD6-AS1 and analyzed its effects on iron ion, ROS, MDA, GSH levels, and SLC7A11/GPX4 expression.
  • Examined HSC activation markers (α-SMA, COL1α1).
  • Investigated the interaction between FRMD6-AS1, miR-491-5p, and USP13.
  • Utilized a carbon tetrachloride (CCl4)-induced liver fibrosis mouse model.

Main Results:

  • FRMD6-AS1 was significantly upregulated in activated HSCs.
  • FRMD6-AS1 knockdown increased ferroptosis markers (iron, ROS, MDA), decreased GSH, and reduced SLC7A11/GPX4 expression.
  • FRMD6-AS1 knockdown suppressed HSC activation markers (α-SMA, COL1α1).
  • FRMD6-AS1 interacted with miR-491-5p, negatively regulating its expression; USP13 was a target of miR-491-5p.
  • The FRMD6-AS1/miR-491-5p/USP13 pathway repressed ferroptosis and promoted ECM deposition, contributing to liver fibrosis.
  • FRMD6-AS1 knockdown ameliorated liver fibrosis in a CCl4 mouse model.

Conclusions:

  • lncRNA FRMD6-AS1 promotes liver fibrosis by inhibiting ferroptosis in HSCs via the miR-491-5p/USP13 pathway.
  • Targeting FRMD6-AS1 may represent a therapeutic strategy for liver fibrosis.