RESUMO
Actin-binding proteins (ABPs) are important components of the F-actin cytoskeleton and affect the dynamics of F-actin by promoting the polymerization and depolymerization of actin. Numerous studies have shown that F-actin and actin-binding proteins are involved in all stages of carcinogenesis. Our analysis of esophageal carcinoma proteomic data showed that the actin-binding protein EHD2 (E p s l 5 homology domain-containing protein 2) is expressed at low levels in esophageal squamous cell carcinoma tissues and patients with lower EHD2 expression had poorer prognosis. Previous studies have revealed that EHD2 is involved in the regulation of glucose metabolism, autophagy and tumor cell migration. However, the role and mechanism of EHD2 in esophageal squamous cell carcinoma progression remain unclear. This study aimed to explore the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. Immunofluorescence and cell fractionation analysis showed that EHD2 was not only localized in the cell membrane and cytoplasm, but also in the nucleus. Colony formation, EdU labeling and flow cytometry were used to determine the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. The results showed that overexpression of EHD2 and EHD2-3×NLS (nuclear localization signal) inhibited proliferation, cell cycle G
RESUMO
Although Signal transducer and activator of transcription 1 (STAT1)-mediated transactivation potential is inhibited in cancer cells, the mechanism is poorly understood. In the present study, we implicated long non-coding RNA lncRNA625 in the inhibition of STAT1 activity. LncRNA625 knockdown up-regulated STAT1-mediated transcription and resulted in an increase of STAT1-mediated expression of IFITM2. Conversely, lncRNA625 upregulation inhibited STAT1 reporter activity. Mechanistically, lncRNA625 inhibited STAT1 binding to the promoter of IFITM2 in both untreated cells and following interferon-gamma (IFN-γ) stimulation. LncRNA625 interacted with the DNA-binding (DB) domain of STAT1 and promoted STAT1 interaction with T-cell protein tyrosine phosphatase TC45 to dephosphorylate pSTAT1. Taken together, the results show that lncRNA625 inhibits STAT1-mediated transactivation potential by causing formation of STAT1-TC45 complexes, resulting in STAT1 dephosphorylation.
