Oct4 regulates the miR-302 cluster in P19 mouse embryonic carcinoma cells

Abstract

Oct4 is a transcription factor that is required for pluripotency during early embryogenesis and the maintenance of embryonic stem (ES) cell and pluripotent cell identity. miR-302, a cluster of eight microRNAs (miRNAs) that are expressed specifically in ES cells and pluripotent cells, is crucial for normal pluripotent cell self-renewal and pluripotency. But, the mechanism by which miR-302 participates in the core regulatory circuitry that controls self-renewal and pluripotency in P19 embryonic carcinoma cells has not been established. Here, we show that Oct4 is required for the expression and transcriptional activation of miR-302 and that Oct4 binds to the putative promoter of miR-302, suggesting that Oct4 activates the primary miR-302 transcript in P19 cells. This study proposes that the miR-302 cluster acts downstream of the Oct4 regulation network in P19 cells.

Hyaluronan-CD44v3 Interaction with Oct4-Sox2-Nanog Promotes miR-302 Expression Leading to Self-renewal, Clonal Formation, and Cisplatin Resistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma

“…A recent study indicates that the promoter of the miR-302 cluster was occupied by key ESC-specific transcriptional factors, including Oct4, Sox2, and Nanog in mouse and human cells (50). Most importantly, the miR-302 family is involved in maintaining stemness of human embryonal carcinoma cells (51) and reprogramming human skin cancer cells to a pluripotent ESC-like state (52). These findings strongly suggest that miR-302 plays an important role in the pluripotency of ESCs and embryonic carcinoma cells.…”

The microRNA-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1

“…Most studies of this cluster have focused on the maintenance of stemness (Card et al 2008;Barroso-del Jesus et al 2009Liu et al 2011;Rosa and Brivanlou 2011) and the ability of the cluster to reprogram somatic cells into induced pluripotent stem cells (iPSCs) (Lin et al 2008Subramanyam et al 2011;Kuo et al 2012;Lipchina et al 2012). In contrast, a recent study demonstrated that the miR-302-367 cluster compromised the maintenance of glioma-initiating cells (GiCs), strongly inhibited the clonogenicity of GiCs and promoted the loss of stem-like proteins, including OCT4 and NANOG, as well as the down-regulation of SOX1 and SHH (Akhavantabasi et al 2012;Fareh et al 2012).…”

Activation of Aryl Hydrocarbon Receptor (AhR) by Tranilast, an Anti-allergy Drug, Promotes miR-302 Expression and Cell Reprogramming

“…But the mechanisms by which miR-302 is regulated are less well understood. Previous studies show that Oct4 and Sox2 co-occupy the promoter region and regulate expression of miR-302; the expression level of miR-302 correlates well with Oct4 transcript in ESCs and early embryonic development (17,18,39). A recent study reports that hyaluronan stimulates the CD44v3 (a hyaluronan receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three transcription factors to promote miR-302 expression, which causes self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma (40).…”

“…MiR-302 is highly expressed in embryonic stem cells (ESCs) (15,16). Recent reports show that pluripotency factors Oct4 and Sox2 bind to the promoter region of miR-302 and tightly regulate miR-302 expression (17,18). The expression level of miR-302 correlates well with the expression level of Oct4 following induction of ESC differentiation (14,18).…”

“…Recent reports show that pluripotency factors Oct4 and Sox2 bind to the promoter region of miR-302 and tightly regulate miR-302 expression (17,18). The expression level of miR-302 correlates well with the expression level of Oct4 following induction of ESC differentiation (14,18). On the other hand, miR-302 functions to regulate cell cycle regulators CDKN1A and RBL2 (19), TGF-␤ signaling negative regulator Lefty1/2 (20), and pluripotency factors Oct4 and Sox2 (21) and thereby contributes to the maintenance of ESC pluripotency.…”