Abstract:
Long non-coding RNAs (lncRNAs) are emerging targets for the diagnosis and therapeutic treatment of cancer. LncRNAs are non-protein-coding transcripts that regulate gene expression by modulating chromatin structure or by interacting with other RNA species. Additionally, they exhibit high tissue- and context-specific expression, marking them as attractive biomarkers. Of the 12,727 lncRNAs identified in human cancers, the vast majority of these remain completely uncharacterized, limiting our understanding of the role of this group of non-coding RNAs. In contrast, the role of protein-coding transcripts as a class has been extensively characterized in cancer biology. To gain insight into the relative impact of lncRNAs in cancer progression in comparison to mRNAs, we conducted a comparative analysis of the two RNA species utilizing patient tumour expression and survival data in 9 cancer types.
Our analysis revealed that lncRNAs exhibit distinct expression patterns across cancers. We determined which lncRNAs are associated with patient outcomes through conducting survival analyses for each lncRNA and mRNA in each cancer type assessed. This determined that lncRNAs are as involved as mRNAs in impacting patient outcomes. Additionally, we found that the function of lncRNAs is highly cancer-dependent, with some lncRNAs playing oncogenic roles in some cancers while exhibiting benign functions in others. Our results indicate that lncRNAs enriched in tumour tissues are more oncogenic, while those depleted in tumor tissues are more tumor suppressive. This study demonstrates that lncRNAs are clinically relevant players in the progression of cancer and merit further investigation as potential therapeutic targets.
