An Insight about Long non-coding RNAs in Colorectal Cancer

Abstract

Background: Long non-coding RNAs (lncRNAs) are a family of non-protein coding RNAs (200 nt-10 kb). They are known to have a crucial role in the regulation of gene expression, alternative splicing mechanisms, protein localization and activity, formation of cellular substructures and protein complexes through their diverse interactions with DNA, RNA and proteins. Deregulation of these molecules has been associated with various human diseases, including cancer, cardiovascular disease, and neurological disorders. Thus, lncRNAs are implicated as potential diagnostic indicators and therapeutic targets. Increasing evidence suggest that lncRNAs are involved in the whole process of CRC development, progression, and metastasis formation - similarly to their diverse regulatory role in other types of malignancies - affecting the essential signaling pathways in CRC . Abnormal expression of numerous lncRNAs including the well-known HOTAIR, MALAT1 and H19 has been described in CRC compared to normal colonic tissue samples. From a clinical point of view, lncRNAs with altered expression in different stages of colorectal carcinogenesis, and disease progression have a particularly great potential to become early diagnostic and/or prognostic biomarkers. Elevated Colon cancer associated transcript-1 (CCAT1)levels could be detected in lymph node and distant liver metastases, as well as in peripheral blood mononuclear cells of CRC patients. Some colorectal cancer associated lncRNAs CRCAL 1-4 were identified as overexpressed and CRC biomarkers using RNA-sequencing techniques. The expression levels of all four CRCALs were found to be elevated in colorectal adenoma samples, as well. RNA interference-mediated knockdown experiments and gene ontology analysis of the Cancer Genome Atlas dataset suggest the involvement of CRCAL-3 and CRCAL-4 in cell cycle regulation.