Recent advances in structural and functional diversities of cancer lncRNA-encoded peptides: current opportunities and challenges for enhancing cancer diagnosis and treatment.

Long non-coding RNAs (lncRNAs) are broad-spectrum cellular transcripts that can directly act as RNA regulators and/or partly encode functional peptides (lncRNA-encoded peptides, LRPs) in cancer cells. Recently, cancer LRPs have been found to be involved in cancer cell variability and proliferation, thus gaining widespread attention for their potential in cancer diagnosis, prognosis and therapy. As structures determine functions, the structural diversities of LRPs are the sources of functional variations of LRPs in cancers. Since 6135 cancer LRPs are listed in SPENCER database and 24 SPENCER-unlisted cancer LRPs are reported in several previous studies, this article reviews recent advances of cancer LRPs, analyzes amino acid compositions of them, and undertakes in silico evaluations to assess their structural and functional attributes. These LRPs are dominated by the amino acids Glu, Leu, and Ser and are rarer in the amino acids Cys, His, and Trp, and that many of the LRPs are rich in secondary or tertiary structures. Like mRNA-encoded peptides, these structure-rich cancer LRPs have a wide range of functions, including anti-cancer, cell-penetrating, anti-inflammatory, and antibacterial activities. Relatively, two groups of anticancer values (predicted by AntiCP 2.0 and PreTP-Stack) of these LRPs commonly showed positive and negative correlations with their total charge content and metal-bind aa content, respectively. The increasing amount of data and analysis on cancer LRPs, as reported here, offers opportunities to enhance practical cancer diagnosis and treatment, and to overcome remaining research challenges for cancer LRPs.