Integrative Analysis of Multi-Omic Data for the Characteristics of Endometrial Cancer

Endometrial cancer (EC) is a frequently diagnosed gynecologic cancer. Identifying reliable prognostic genes for predicting EC onset is crucial for reducing patient morbidity and mortality. Here, a comprehensive strategy with transcriptomic and proteomic data was performed to measure EC’s characteristics. Based on the publicly available RNA-seq data, death-associated protein kinase 3, recombination signal-binding protein for the immunoglobulin kappa J region, and myosin light chain 9 were screened out as potential biomarkers that affect the EC patients’ prognosis. A linear model was further constructed by multivariate Cox regression for the prediction of the risk of being malignant. From further integrative analysis, exosomes were found to have a highly enriched role that might participate in EC occurrence. The findings were validated by qRT-polymerase chain reaction (PCR) and western blotting. Collectively, we constructed a prognostic-gene-based model for EC prediction and found that exosomes participate in EC incidents, revealing significantly promising support for the diagnosis of EC

Structural Basis of Inhibition of ERα-Coactivator Interaction by High-Affinity N‑Terminus Isoaspartic Acid Tethered Helical Peptides

Direct inhibition of the protein–protein interaction of ERα and its endogenous coactivators with a cell permeable stabilized peptide may offer a novel, promising strategy for combating ERα positive breast cancers. Here, we report the co-crystal structure of a helical peptide stabilized by a N-terminal unnatural cross-linked aspartic acid (<b>TD</b>) in complex with the ERα ligand binding domain (LBD). We designed a series of peptides and peptide <b>6</b> that showed direct and high-affinity binding to ERα with selective antiproliferative activity in ERα positive breast cancer cells. The co-crystal structure of the <b>TD</b>-stabilized peptide <b>6</b> in complex with ERα LBD further demonstrates that it forms an α helical conformation and directly binds at the coactivator binding site of ERα. Further studies showed that peptide <b>6</b>_<b>W</b> could potently inhibit cellular ERα’s transcriptional activity. This approach demonstrates the potential of <b>TD</b> stabilized peptides to modulate various intracellular protein–protein interactions involved in a range of disorders