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Updated: May 25, 2026
11:44
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration
Raymond Ng1, Guisheng Song, Garrett R Roll
1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, UCSF, San Francisco, California 94143, USA.
The Journal of Clinical Investigation
|February 14, 2012
Summary
MicroRNA-21 (miR-21) accelerates liver regeneration by promoting hepatocyte cell cycle progression. Inhibiting miR-21 slows liver repair by decreasing cyclin D1 translation, impacting proliferation.
Area of Science:
- Molecular Biology
- Cell Biology
- Hepatology
Background:
- MicroRNA-21 (miR-21) is recognized as an oncomir, promoting cancer progression.
- The physiological role of miR-21 in normal cells, particularly hepatocytes, remains unclear.
- miR-21 expression is rapidly upregulated in rodent hepatocytes during liver regeneration following partial hepatectomy (PH).
Purpose of the Study:
- To investigate the function of miR-21 in regenerating mouse hepatocytes.
- To determine the impact of miR-21 inhibition on hepatocyte cell cycle progression and proliferation during liver regeneration.
Main Methods:
- Utilized antisense oligonucleotides to inhibit miR-21 in regenerating mouse livers after two-thirds partial hepatectomy (2/3 PH).
- Maintained normal hepatocyte viability and function by antagonizing the miR-21 surge while preserving baseline expression.
- Assessed hepatocyte progression into the S phase of the cell cycle and measured levels of cyclin D1 protein and Ccnd1 mRNA.
Main Results:
- Knockdown of miR-21 impaired hepatocyte progression into S phase during liver regeneration.
- This impairment was primarily attributed to a decrease in cyclin D1 protein levels, not Ccnd1 mRNA.
- miR-21 was found to facilitate cyclin D1 translation by relieving Akt1/mTOR complex 1 signaling suppression by Rhob.
Conclusions:
- miR-21 plays a crucial role in enabling rapid hepatocyte proliferation during liver regeneration.
- miR-21 accelerates liver repair by enhancing cyclin D1 translation, a key driver of cell cycle progression.
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