ECE1 (Endothelin Converting Enzyme 1)

Biocomputational analyses from non-AD controls and individuals with AD pathology showed that the highest messenger ribonucleic acid (mRNA) levels of ECE1 expression were found in pericytes (i.e., cells within the brain microvasculature that are known to produce Aβ34) compared to other cell types. Given Aβ34 is an indicator for prodromal AD, we postulate that our collective findings (i.e., generation of Aβ34 and Aβ20-34 intermediates within the "amyloidolytic" degradation pathway) will generate a set of biomarkers to detect amyloid clearance activity in vivo.

In this study, the ECE1 gene was cloned from the Lethenteron reissneri, and bioinformatics analysis showed that it had a high degree of similarity with the ECE1 of jawed vertebrates. This discovery provides important clues for exploring the role of ECE1 in lamprey biology, especially its potential functions in signal transduction, nervous system, cardiovascular system, digestive system, and immune diseases.

The results suggest the significant role of candidalysin in oral oncogenesis. The high odds and risk ratio specify a strong association between candidalysin and these conditions. Screening this gene in a large number of isolates would further reinforce their role in oncogenesis. Future studies in characterizing their virulence on normal cell lines would clarify the importance of candidalysin in promoting oncogenesis.

Furthermore, HIF1A upregulated the transcription of ECE1 through binding to its promoter region. HIF1A might expedite cholesteatoma keratinocyte proliferation partly by increasing ECE1 expression, providing a possible therapeutic target for the cholesteatoma treatment.

The present study reveals a non-canonical function of ECE1 in regulating AKT activation and cell proliferation, which provides the basis for the development of a novel strategy for the intervention of cancer including LUAD by abrogating ECE1-AKT signaling.