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Related Concept Videos

MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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MicroRNA-29a-3p Prevents Drug-Induced Acute Liver Failure through Inflammation-Related Pyroptosis Inhibition.

Dan-Dan Xiang1, Jing-Tao Liu2, Zi-Biao Zhong3

  • 1Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Current Medical Science
|April 28, 2023
PubMed
Summary

MicroRNA-29a-3p (miR-29a-3p) protects against drug-induced acute liver failure (DIALF) by inhibiting inflammation-related pyroptosis via the PI3K/AKT pathway. Lower miR-29a-3p levels are observed in DIALF patients, suggesting its therapeutic potential.

Keywords:
acute liver failureinflammationmicroRNA-29a-3ppyroptosis

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Area of Science:

  • Molecular Biology
  • Hepatology
  • Immunology

Background:

  • Drug-induced acute liver failure (DIALF) pathogenesis involves inflammation and pyroptosis.
  • The role of microRNA-29a-3p (miR-29a-3p) in DIALF and pyroptosis remains largely unknown.

Purpose of the Study:

  • To investigate the relationship between miR-29a-3p and inflammation-related pyroptosis in DIALF.
  • To elucidate the underlying molecular mechanisms of miR-29a-3p in DIALF.

Main Methods:

  • Established thioacetamide (TAA)- and acetaminophen (APAP)-induced DIALF mouse models and utilized human samples.
  • Quantified miR-29a-3p, inflammation, and pyroptosis markers using qRT-PCR, Western blotting, and immunochemical staining.
  • Employed RNA sequencing in miR-29a-3p knock-in transgenic mice (MIR29A(KI/KI)) to explore mechanisms.

Main Results:

  • miR-29a-3p levels were significantly decreased in TAA- and APAP-induced DIALF models.
  • Overexpression of miR-29a-3p demonstrated a protective effect against TAA- and APAP-induced DIALF.
  • RNA sequencing revealed that miR-29a-3p inhibits inflammation-related pyroptosis by activating the PI3K/AKT pathway.
  • Reduced miR-29a-3p and activated pyroptosis were observed in DIALF patients' peripheral blood mononuclear cells and liver tissues.

Conclusions:

  • miR-29a-3p exerts a protective role in DIALF by suppressing pyroptosis through PI3K/AKT pathway activation.
  • miR-29a-3p represents a potential therapeutic target for managing DIALF.