MicroRNA-34c is important for the first cell division in mouse embryos

Abstract

Mature microRNAs (miRNAs) are noncoding RNAs with ~22 nucleotides. They regulate biological processes by gene silencing and/or transcript degradation. While evidences suggest involvement of miRNAs in early embryo development, the mechanisms of action are largely unclear. Here, we reported the miRNA expression profile of mouse preimplantation embryos using multiplex real-time polymerase chain reaction, and noted stage-specific expression of miRNAs during development. We identified 16 miRNAs that were up-regulated only at the zygotic stage. MiR-34c was one of them. Its expression in the oocytes was weak but increased 4-fold in the zygotes. Microinjection of miR-34c inhibitor, but not non-specific miRNA inhibitor, suppressed DNA synthesis and significant inhibited the first cell division of zygotes. MiR-34c regulated the expression of Bcl-2 in the mouse zygotes and a human trophoblast cell line as shown by 3’UTR luciferase assay and Western blotting with or without microinjection of miR-34c inhibitor. The effect of miR-34c inhibition was partially nullified by microinjection of anti-Bcl-2 antibody. On the other hand, microinjection of Bcl-2 protein mimics the action of miR-34c inhibitor. In addition, microinjection of either miR-34c inhibitor or Bcl-2 reduced c-myc expression. In conclusion, miR-34c regulated the first cell division partially via Bcl-2.