Rhabdomyosarcoma (RMS), a common malignant tumor in children, presents numerous challenges in clinical treatment. This study investigated the specific functions and regulatory mechanisms of distal-less homeobox 5 ( DLX5 ) in RMS. Data from TCGA, GEO and GEPIA databases were downloaded and analyzed. The effect of DLX5 and PAX3-FOXO1 on RMS cells was examined through cellular experiments. Binding activity between DLX5 and H3K9me2 was assessed using pull-down and chromatin immunoprecipitation-qPCR assays. Additionally, RMS model mice were constructed via xenotransplantation to validate the in vivo effects of DLX5 on RMS. The results revealed that DLX5 was upregulated in RMS tissues and increased in various RMS cell lines, particularly in alveolar RMS cell lines. DLX5 knockdown inhibited malignant biological behaviors. Besides, DLX5 expression was associated with myogenic differentiation of RMS cells. While the overexpression or knockdown of DLX5 did not affect PAX-FOXO1 expression. PAX3-FOXO1 knockdown reduced DLX5 expression, indicating that DLX5 act as a downstream effector of PAX3-FOXO1 . Mechanistically, PAX3-FOXO1 regulated DLX5 expression through KDM4B/H3K9me2 axis. In vitro experiments further demonstrated that knockout of DLX5 or KDM4B inhibited tumor growth. In conclusion, DLX5 expression was increased in PAX3-FOXO1 –driven RMS, and its knockdown inhibited malignant biological behaviors of RMS cells. Moreover, the aberrant expression of DLX5 in PAX3-FOXO1 –driven RMS was regulated by KDM4B/H3K9me2 axis. These findings provided potential therapeutic targets for RMS treatment.
QiuShi Wei,MinCong He,MeiHui Chen,ZhenQiu Chen,Fan Yang,HaiBin Wang,Jin Zhang,Wei He
Icariin, the major ingredient of Herba Epimedii, promotes the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and exerts protective effects against bone loss and increases bone regeneration, but the underlying signaling pathway by which icariin affects osteogenic differentiation remain unclear. Transcriptional coactivator with PDZ-binding motif (TAZ) is a transcriptional modulator of the Hippo signaling pathway, which plays an important role in the osteogenic differentiation of BMSCs by activating Runx2 gene during the terminal osteogenic differentiation. In this study, we found that 0.1 μM icariin markedly promoted the proliferation, calcium depositions, and osteogenic genes expression of rBMSCs. Icariin (0.1 μM) upregulated TAZ, Runx2, β-catenin, Osteopotin, and Dlx5 expression mainly at the early stage of osteogenic differentiation, and increased osteocalcin expression at the late stage. Our result further demonstrated that knockdown TAZ expression by lentivirus-mediated TAZ shRNA inhibited the icariin-induced osteogenic differentiation. Moreover, ICI 182780 (the estrogen receptor alpha inhibitor) or DKK1 (the Wnt/β-catenin pathway inhibitor), inhibited the icariin-induced increase in TAZ expression. Furthermore, icariin stimulated the activation of TAZ as evidenced by increased total TAZ protein and nuclear translocation, but these effects of icariin were blocked by ICI 182780 or DKK1. Taken together, our results demonstrate that icariin promotes the osteogenic differentiation of rBMSCs by increasing TAZ expression, and that the increased TAZ expression induced by icariin is mostly mediated by the ERα and Wnt/β-catenin pathway.
危险品化学品经营许可证（带存储）