Functional Analysis Of Rmnd5a/rmnd5b In Human Heart Development And Carcinogenesis Genes

Cardiovascular diseases and cancer have become two of the most serious diseases that threate human beings. Cardiovascular diseases, especially angiocardiopathy, almost one third persons accounted for human disease killed and the ratio of the cancer occurrence in the crowd grow fast. It is a critical to understand the normal progress of cardiovascular development , carcinogenesis and the mechanisms underlying the causes of these kinds of diseasesThe preliminary research proved human embryo expression of RMND5A and RMND5B. The aim of this research was to further understand what they were involved in signaling pathway.By the interaction of a large-scale screening and bioinformatic analysis, I found some interaction proteins of RMND5B and RMND5A . Through co-immunoprecipitation and the subcellular localization, I identified three pairs of interaction proteins: RMND5A and RMND5B RMND5B and SMAD3, SMAD4 and RMND5B.Fluorescence studies showed that RMND5A and RMND5B in HEK293 cells mainly localized in the cytoplasm, and their CRA domain showed the same location with the full-lenth of the genes.Luciferase report assay showed that RMND5A and RMND5B were involved in the SMAD signaling pathway. RMND5A strongly inhibited TGFβrelated signaling pathway and RMND5B strongly inhibited TGFβand BMP signaling pathways.RMND5B also inhibited the activity of SMAD3 in TGFβsignaling pathway.We established a mouse model of cardiac hypertrophy. RT-PCR showed that RMND5B expression had notable differences in cardiac hypertrophy mice and in control. By the situ hybridization in mouse embryos and heart of the newborn mice. we can further study in the heart of the RMND5B expression .It had a great significance for knockout mice expressed research.RT-PCR analyses showed that the expression of RMND5A and RMND5B were quite different in normal tissue and cancer tissues. RMND5A and RMND5B strongly inhibited the fluorescence activities of the p21 and p53 proteins.In sum up, we found that RMND5A and RMND5B were involved in Smad signaling pathway and influence heart development and carcinogenesis...