A short peptide encoded by long non‐coding RNA small nucleolar RNA host gene 6 promotes cell migration and epithelial–mesenchymal transition by activating transforming growth factor‐beta/SMAD signaling pathway in human endometrial cells

Abstract Background Endometrial dysfunction is closely correlated with the development of multiple severe gynecological disorders including intrauterine adhesion. Accumulating evidence supports that some long non‐coding RNAs (lncRNAs) have peptide‐coding potential. In this text, the peptide‐coding ability of lncRNA SNHG6 was examined. Also, the effects of an SNHG6‐encoded peptide on the viability and migration of human endometrial stromal cells (hESCs) and human endometrial epithelial cells (hEECs) and related molecular mechanisms were explored. Methods The peptide‐encoding potential of SNHG6 was predicted by FuncPEP and getorf databases and validated by western blot assay. Cell viability was tested by cell counting kit‐8 assay. Cell migratory ability was examined by wound healing and transwell migration assays. Protein levels of genes were measured by western blot assay. Results Prediction analysis suggested that SNHG6 had the potential peptide‐coding ability and multiple open‐reading frames (ORFs). Western blot validated that SNHG6 ORF#1 and ORF#2 could translate into short peptides. SNHG6 ORF#2 overexpression facilitated cell migration and epithelial–mesenchymal transition (EMT) in hESCs and hEECs, while these effects were abrogated by transforming growth factor‐beta (TGF‐β)/SMAD signaling inhibitor GW788388. Moreover, GW788388 inhibited the increase of p‐SMAD2 and p‐SMAD3 levels induced by SNHG6 ORF#2 in hESCs. SNHG6 ORF#2‐encoded peptide did not influence endometrial stromal and epithelial cell viability. Conclusions LncRNA SNHG6 ORF#1 and ORF#2 could translate into small peptides and SNHG6 ORF#2 overexpression promoted cell migration and EMT by activating the TGF‐β/SMAD pathway in hESCs and hEECs, suggesting the potential roles of SNHG6‐encoded peptides in the development of endometrial stromal and epithelial cells and related gynecological diseases.