Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2

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.

E2F1 Mediates the Retinoic Acid-Induced Transcription of Tshz1 during Neuronal Differentiation in a Cell Division-Dependent Manner

ABSTRACT The involvement of cell division in cellular differentiation has long been accepted. Cell division may be required not only for the expansion of a differentiated cell population but also for the execution of differentiation processes. Nonetheless, knowledge regarding how specific differentiation processes are controlled in a cell division-dependent manner is far from complete. Here, we determined the involvement of cell division in neuronal differentiation. We initially confirmed that cell division is an essential event for the neuronal differentiation of P19 embryonic carcinoma cells. We investigated the induction mechanisms of Tshz1, whose expression is induced by retinoic acid (RA) in a cell division-dependent manner. Promoter analysis of Tshz1 revealed a specific region required for RA-dependent transcription. A series of experiments was used to identify E2F1 as the induction factor for the RA-dependent transcription of Tshz1. We propose that E2F1 mediates neuronal differentiation in a cell division-dependent manner.