A MicroRNA-21 Surge Facilitates Rapid Cyclin D1 Translation and Cell Cycle Progression in Mouse Liver Regeneration.
- Author(s): Ng, Raymond
- Advisor(s): Willenbring, Holger
- et al.
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.