Glioma is a lethal malignant
brain cancer, and many reports have shown that abnormalities in the behavior of water and
ion channels play an important role in regulating
tumor proliferation, migration, apoptosis, and differentiation. Recently, new studies have suggested that some long noncoding RNAs containing small open reading frames can encode small
peptides and form oligomers for water or ion regulation. However, because the
peptides are difficult to identify, their functional mechanisms are far from being clearly understood. In this study, we used bioinformatics methods to identify and evaluate lncRNAs, which may encode small transmembrane
peptides in
gliomas. Combining ab initio homology modeling, molecular dynamics simulations, and free energy calculations, we constructed a predictive model and predicted the oligomer channel activity of
peptides by identifying the
lncRNA ORFs. We found that one key hub
lncRNA, namely, DLEU1, which contains two smORFs (ORF1 and ORF8), encodes small
peptides that form pentameric channels. The mechanics of water and ion (Na+ and Cl-) transport through this pentameric channel were simulated. The potential mean force of the H2O molecules along the two ORF-encoded
peptide channels indicated that the energy barrier was different between ORF1 and ORF8. The ORF1-encoded
peptide pentamer acted as a self-assembled
water channel but not as an
ion channel, and the ORF8 permeated neither
ions nor water. This work provides new methods and theoretical support for further elucidation of the function of
lncRNA-encoded small
peptides and their role in
cancer. Additionally, this study provides a theoretical basis for
drug development.