Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation.

Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced microRNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these pro-differentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.

[Interchangeability of resin composites and bonding agents based on bis-GMA or UDMA].

Recently, dentin bonding systems have been released separately from the resin composites, because the adhesive systems have been quickly improved. Since the merit of each material should be effectively utilized for each clinical case, the bonding systems and resin composites produced by different manufacturers may be combined according to the clinical purpose. The current restorative resins are basically categorized into two groups according to the main resin monomer, bis-GMA or UDMA resins. The purpose of this study was to evaluate the interchangeability between the bonding systems and resin composites, which were made by different manufacturers. Two bonding systems and five resin composites based on bis-GMA or UDMA were used in this study. The evaluation was performed by the tensile bond strength, fracture modes, and SEM observation, using the dentin surface of freshly-extracted bovine teeth. The highest bond strength (19.2 MPa) was shown by the combination of LBII sigma and AP-X. The bond strengths of nine other combinations were not statistically different (p > 0.05). There were many cohesive failures in dentin or resin composite, using all combinations. From the results, it was concluded that the interchangeability of the resin composites and bonding systems should be clinically acceptable.