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A MicroRNA-21 Surge Facilitates Rapid Cyclin D1 Translation and Cell Cycle Progression in Mouse Liver Regeneration.


MicroRNA-21 (miR-21) has been labeled as an oncomir because it promotes

cancer cell proliferation, migration and survival. miR-21 is also expressed in normal

cells, however its physiological role is poorly understood. Recently, we found that miR-

21 expression is rapidly induced in hepatocytes during liver regeneration after 2/3

partial hepatectomy (2/3 PH). Here, we investigated miR-21's function in

regenerating hepatocytes by inhibiting it with an antisense oligonucleotide. To

ascertain normal hepatocyte viability and function, we antagonized the miR-21

surge induced by 2/3 PH while preserving baseline expression. We found that

knockdown of miR-21 impaired progression of hepatocytes into S phase of the cell

cycle mainly through a decrease in cyclin D1 protein but not mRNA. As for the

underlying mechanism, we discovered that increased miR-21 expression facilitates

cyclin D1 translation in the early phase of liver regeneration by relieving

Akt1/mTOR complex 1 signaling and thus eIF-4F-mediated translation initiation

from suppression by Rhob. Our findings reveal that miR-21 accelerates cyclin D1

translation in hepatocytes, thereby enabling rapid liver regeneration.

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