Yaf2 inhibits Myc biological function
CANCER LETTERS
Authors: Madge, B; Geisen, C; Moroy, T; Schwab, M
Abstract
The proto-oncogenes of the myelocytomatosis viral oncogene homolog (MYC) family, including MYC, MYCN and MYCL, encode nuclear proteins that act as transcription factors. The Myc protein is the best studied member of this family and is involved in cell cycle regulation, differentiation and cell death. We have previously demonstrated that the zinc-finger protein Yaf2 interacts with the central region of MycN and enhances MycN dependent transcriptional activation. Here we show that Yaf2 also binds to the Myc protein in vivo and in vitro. In contrast to the activating effect on MycN function, Yaf2 inhibits Myc mediated transactivation and transformation. This differential influence on two members of the Myc family gives insight into a new mechanism to modulate the biological activities of Myc transcription factors. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
MicroRNA-543 promotes ovariectomy-induced osteoporosis through inhibition of AKT/p38 MAPK signaling pathway by targeting YAF2
JOURNAL OF CELLULAR BIOCHEMISTRY
Authors: Li, Xiang; Ning, Lei; Zhao, Xiangde; Wan, Shuanglin
Abstract
The present study aimed to determine the roles of miRNA-543 in osteoporosis in rats induced by ovariectomy. The osteoporosis rat model was established by ovariectomy induction. MiRNA-543 expression in osteoblasts was measured by quantitative real-time polymerase chain reaction. The cell proliferation and apoptosis were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays, respectively. Western blot analysis was conducted to examine the expression of YAF-2 and AKT signaling. TargetScan analysis and dual-luciferase reporter assay were performed to determine the target gene of miRNA-543. MiRNA-543 was significantly upregulated in osteoporosis rat model. Overexpression of miRNA-543 significantly suppressed cell growth and promoted apoptosis in osteoblasts, whereas downregulation of miRNA-543 significantly enhanced cell growth and inhibited apoptosis. MiRNA-543 upregulation significantly inhibited YAF-2 expression and suppressed the phosphorylation and expression of AKT and p38 mitogen-activated protein kinases (MAPK) in osteoblasts. Furthermore, YAF-2 knockdown enhanced the effects of miRNA-543 on apoptosis in osteoblasts. AKT inhibitor MK2206 and p38 MAPK inhibitor SB203580 also enhanced the effects of miRNA-543 on apoptosis in osteoblasts. Our findings revealed that inhibition of miRNA-543 could protect osteoblasts against ovariectomy-induced osteoporosis through AKT/p38 MAPK signaling pathway by targeting YAF2.