Human LEF1 peptide

Acute myeloid leukemia (AML) is a malignant clonal disorder affecting myeloid differentiation through mechanisms that include epigenetic dysregulation. Abnormal changes in DNA methylation and gene expression profiles of pathways involved in hematopoietic development, such as Wnt/beta-catenin, contribute to the transformation, development, and maintenance of leukemic cells. This review summarizes the alterations of Wnt signaling-related genes at the epigenetic and transcriptional level and their implications for AML prognosis. Among the implications of epigenetic alterations in AML, methylation of Wnt antagonists is related to poor prognosis, whereas their upregulation has been associated with a better clinical outcome. Furthermore, Wnt target genes c-Myc and LEF-1 present distinct implications. LEF-1 expression positively influences the patient overall survival. c-Myc upregulation has been associated with treatment resistance in AML, although c-Myc expression is not exclusively dependent of Wnt signaling. Understanding the signaling abnormalities could help us to further understand leukemogenesis, improve the current risk stratification for AML patients, and even serve to propose novel therapeutic targets.

Background Increasing evidence indicates that long non-coding RNAs (lncRNAs) play crucial regulatory roles in epithelial-mesenchymal transition (EMT). However, the regulatory mechanisms during EMT of the medial edge epithelium (MEE) remain elusive. The aim of this work is to reveal a novel lncRNA-regulated dysfunction of EMT involved in the development of cleft palate (CP). Methods C57BL/6 J mice at embryonic gestation day 14.5 (n = 6, 3 case samples vs. 3 control samples) were used to establish the CP model for lncRNA-mRNA co-expression profile analysis after high-throughput sequencing. Functional predictions for the differentially expressed lncRNA-mRNA co-expression with transcription factor (TF)-target gene relationship Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway (GO/KEGG) analyses identified the regulatory "lncRNA-TF-target gene" trans model. Results A total of 583 differentially expressed lncRNAs and 703 differentially expressed mRNAs were identified. The results of trans analysis revealed that some TFs (LEF1, SMAD4, and FOXD3) regulate lncRNAs and gene expression. Finally, we identified the NONMMUT034790.2-LEF1-SMAD7 co-expression trans-regulatory network that might be associated with CP. Conclusions Our results revealed that NONMMUT034790.2 might be a novel epigenetic biomarker in CP. The integration of lncRNA modulators into trans-regulatory networks will further enhance our understanding of lncRNA functions and regulatory mechanisms during palatal fusion in ATRA-induced mouse CP.