Comprehensive identification of long noncoding RNAs in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most common cancers in humans and a leading cause of cancer-related deaths worldwide. As in the case of other cancers, CRC heterogeneity leads to a wide range of clinical outcomes and complicates therapy. Over the years, multiple factors have emerged as markers of CRC heterogeneity, improving tumor classification and selection of therapeutic strategies. Understanding the molecular mechanisms underlying this heterogeneity remains a major challenge. A considerable research effort is therefore devoted to identifying additional features of colorectal tumors, in order to better understand CRC etiology and to multiply therapeutic avenues. Recently, long noncoding RNAs (lncRNAs) have emerged as important players in physiological and pathological processes, including CRC. Here we looked for lncRNAs that might contribute to the various colorectal tumor phenotypes. We thus monitored the expression of 4898 lncRNA genes across 566 CRC samples and identified 282 lncRNAs reflecting CRC heterogeneity. We then inferred potential functions of these lncRNAs. Our results highlight lncRNAs that may participate in the major processes altered in distinct CRC cases, such as WNT/β-catenin and TGF-β signaling, immunity, the epithelial-to-mesenchymal transition (EMT), and angiogenesis. For several candidates, we provide experimental evidence supporting our functional predictions that they may be involved in the cell cycle or the EMT. Overall, our work identifies lncRNAs associated with key CRC characteristics and provides insights into their respective functions. Our findings constitute a further step towards understanding the contribution of lncRNAs to CRC heterogeneity. They may open new therapeutic opportunities.