Abstract
Retinoic acid (RA) plays a key role in pluripotent cell differentiation. In F9 embryonic carcinoma cells, RA can induce differentiation towards somatic lineages via the Ras-extracellular signal-regulated kinase (Ras/Erk) pathway, but the mechanism through which it induces the Erk1/2 phosphorylation is unclear. Here, we show that miR-485 is a positive regulator that targets α/β-hydrolase domain-containing protein 2 (Abhd2), which can result in Erk1/2 phosphorylation and triggers differentiation. RA up-regulates miR-485 and concurrently down-regulates Abhd2. We verified that Abhd2 is targeted by miR-485 and they both can influence the phosphorylation of Erk1/2. In summary, RA can mediate cell differentiation by phosphorylating Erk1/2 via miR-485 and Abhd2.
Highlights
The ability to differentiate into all cell types is an important characteristic of embryonic stem cells (ESCs) that can be used for the treatment of diseases [1,2]
PD is one of the inhibitors that inhibits the enhancement of Erk1/2 phosphorylation by fibroblast growth factor-4 (FGF4) stimulation in mouse embryonic stem cells (mESCs), which occurs through the mitogen-activated protein kinase and mitogen-activated protein kinase (MAPK/Extracellular signal-regulated kinase (Erk)) pathway [17,18]
It can restrict the differentiation of ESCs by inactivating MAPK/Erk and in our previous study, we showed that PD antagonizes retinoic acid (RA)-induced differentiation in mESCs and F9 ECs
Summary
The ability to differentiate into all cell types is an important characteristic of embryonic stem cells (ESCs) that can be used for the treatment of diseases [1,2]. PD is one of the inhibitors that inhibits the enhancement of Erk1/2 phosphorylation by fibroblast growth factor-4 (FGF4) stimulation in mESCs, which occurs through the mitogen-activated protein kinase and mitogen-activated protein kinase (MAPK/Erk) pathway [17,18] It can restrict the differentiation of ESCs by inactivating MAPK/Erk and in our previous study, we showed that PD antagonizes RA-induced differentiation in mESCs and F9 ECs. numerous reports have indicated that RA induces cell differentiation mainly through the MAPK/Erk pathway [7,16,19]. MicroRNAs (miRNAs) are small noncoding RNAs that consists of 21–25 nucleotides and are assembled into RNA-induced silencing complexes, which target mRNAs for silencing via the base pairing of the miRNA sequence and mRNA 3 untranslated region (3 -UTR ) They are evolutionarily conserved and play important roles in differentiation [24,25]. These findings imply that RA promotes F9 EC cell differentiation at least partly through miR-485 via Abhd2-regulated Erk1/2 phosphorylation
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