The oncogenic role of EIF4A3/CDC20 axis in the endometrial cancer.

Eukaryotic initiation factor 4A-3 (EIF4A3) is a key component of the exon junction complex (EJC) and is extensively involved in RNA splicing, inducing mRNA decay, and regulating the cell cycle and apoptosis. However, the potential role of EIF4A3 in EC has not been comprehensively investigated and remains unknown. Here, we report that the expression level of EIF4A3 is dramatically elevated in endometrial cancer (EC) samples compared with normal EC samples via bioinformatics analysis and immunohistochemistry analysis, and that high expression of EIF4A3 promotes the proliferation, migration, and invasion of EC cells. Mechanistically, we found that high EIF4A3 expression stabilized cell division cyclin 20 (CDC20) mRNA, and high EIF4A3 expression induced pro-carcinogenic effects in EC cells that were efficiently antagonized upon knockdown of CDC20, as well as Apcin, an inhibitor of CDC20. These findings reveal a novel mechanism by which high expression of EIF4A3 induces CDC20 upregulation, thus leading to EC tumorigenesis and metastasis, indicating a potential treatment strategy for EC patients with high EIF4A3 expression using Apcin. KEY MESSAGES: The expression level of EIF4A3 was dramatically elevated in endometrial cancer (EC) samples compared with normal endometrial cancer samples. High EIF4A3 expression stabilized CDC20 mRNA, and high EIF4A3 expression induced pro-carcinogenic effect in EC cells which was efficiently antagonized upon knockdown of CDC20. Apcin, an inhibitor of CDC20, could effectively counteract high expression of EIF4A3 inducing EC tumourigenesis and metastasis, indicating the potential treatment strategy for EC patients with EIF4A3 high expression by using Apcin.

The roles of FLOT1 in human diseases (Review).

FLOT1, a scaffold protein of lipid rafts, is involved in several biological processes, including lipid raft protein­-dependent or clathrin­independent endocytosis, and the formation of hippocampal synapses, amongst others. Increasing evidence has shown that FLOT1 can function as both a cancer promoter and cancer suppressor dependent on the type of cancer. FLOT1 can affect the occurrence and development of several types of cancer by affecting epithelial­mesenchymal transition, proliferation of cancer cells, and relevant signaling pathways, and is regulated by long intergenic non­coding RNAs or microRNAs. In the nervous system, overexpression or abnormally low expression of FLOT1 may lead to the occurrence of neurological diseases, such as Alzheimer's disease, Parkinson's disease, major depressive disorder and other diseases. Additionally, it is also associated with dilated cardiomyopathy, pathogenic microbial infection, diabetes­related diseases, and gynecological diseases, amongst other diseases. In the present review, the structure and localization of FLOT1, as well as the physiological processes it is involved in are reviewed, and then the upstream and downstream regulation of FLOT1 in human disease, particularly in different types of cancer and neurological diseases are discussed, with a focus on potentially targeting FLOT1 for the clinical treatment of several diseases.

The crosstalk between ubiquitination and endocrine therapy.

Endocrine therapy (ET), also known as hormone therapy, refers to the treatment of tumors by regulating and changing the endocrine environment and hormone levels. Its related mechanism is mainly through reducing hormone levels and blocking the binding of hormones to corresponding receptors, thus blocking the signal transduction pathway to stimulate tumor growth. However, with the application of ET, some patients show resistance to ET, which is attributed to abnormal accumulation of hormone receptors (HRs) and the production of multiple mutants of HRs. The targeted degradation of abnormal accumulation protein mediated by ubiquitination is an important approach that regulates the protein level and function of intracellular proteins in eukaryotes. Here, we provide a brief description of the traditional and novel drugs available for ET in this review. Then, we introduce the link between ubiquitination and ET. In the end, we elaborate the clinical application of ET combined with ubiquitination-related molecules. KEY MESSAGES: • A brief description of the traditional and novel drugs available for endocrine therapy (ET). • The link between ubiquitination and ET. • The clinical application of ET combined with ubiquitination-related molecules.

Selection of Secondary Structures of Heterotypic Supramolecular Peptide Assemblies by an Enzymatic Reaction.

In a model study to investigate the consequence of reactions of intrinsically disordered regions (IDRs) of proteins in the context of the formation of highly ordered structures, we found that enzymatic reactions control the secondary structures of peptides during assembly. Specifically, phosphorylation of an α-helix-dominant peptide results in mostly disordered conformations, which become ß-strand-dominant after enzymatic dephosphorylation to regenerate the peptide. In the presence of another peptide largely with a ß-strand conformation, direct coassembly of the peptides results in amorphous aggregates consisting of α-helix and ß-strand peptides, but the enzymatically generated peptide coassemblies (from the phosphopeptide) mainly adopt a ß-strand conformation and form ordered structures (e.g., nanofibers). These results indicate that enzymatic dephosphorylation instructs conformationally flexible peptides to adopt thermodynamically favorable conformations in homotypic or heterotypic supramolecular assemblies.