Non-coding landscapes of colorectal cancer

Abstract

For two decades Vogelstein's model has been the paradigm for describing the sequence of molecular changes within protein-coding genes that would lead to overt colorectal cancer (CRC). This model is now too simplistic in the light of recent studies, which have shown that our genome is pervasively transcribed in RNAs other than mRNAs, denominated non-coding RNAs (ncRNAs). The discovery that mutations in genes encoding these RNAs [i.e., microRNAs (miRNAs), long non-coding RNAs, and circular RNAs] are causally involved in cancer phenotypes has profoundly modified our vision of tumour molecular genetics and pathobiology. By exploiting a wide range of different mechanisms, ncRNAs control fundamental cellular processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis: these data have also confirmed their role as oncogenes or tumor suppressors in cancer development and progression. The existence of a sophisticated RNA-based regulatory system, which dictates the correct functioning of protein-coding networks, has relevant biological and biomedical consequences. Different miRNAs involved in neoplastic and degenerative diseases exhibit potential predictive and prognostic properties. Furthermore, the key roles of ncRNAs make them very attractive targets for innovative therapeutic approaches. Several recent reports have shown that ncRNAs can be secreted by cells into the extracellular environment (i.e., blood and other body fluids): this suggests the existence of extracellular signalling mechanisms, which may be exploited by cells in physiology and pathology. In this review, we will summarize the most relevant issues on the involvement of cellular and extracellular ncRNAs in disease. We will then specifically describe their involvement in CRC pathobiology and their translational applications to CRC diagnosis, prognosis and therapy.

Long non‐coding RNA PCAT6 targets miR‐204 to modulate the chemoresistance of colorectal cancer cells to 5‐fluorouracil‐based treatment through HMGA2 signaling

“…Some lncRNAs have primarily been found to be associated with tumor invasion, metastasis, and even multi‐drug resistance . For example, lncRNA H19 works as an miRNA precursor of miR‐675 and an endogenous miRNA sponge of let‐7 to affect CRC cell proliferation and EMT . LncRNA prostate cancer‐associated transcript 6 (PCAT6) (also known as PCAN‐R1, ncRNA‐a2, and KDM5B‐AS1) was first identified in keratinocytes and indirectly activates the Wnt/β‐catenin pathway by interacting with KLHL12 in cervical cancer cells .…”

“…19,24,25 For example, lncRNA H19 works as an miRNA precursor of miR-675 and an endogenous miRNA sponge of let-7 to affect CRC cell proliferation and EMT. 26 LncRNA prostate cancer-associated transcript 6 (PCAT6) (also known as PCAN-R1, ncRNA-a2, and KDM5B-AS1) was first identified in keratinocytes and indirectly activates the Wnt/β-catenin pathway by interacting with KLHL12 in cervical cancer cells. 27 With the use of lncRNA microarray, PCAT6 was further confirmed as the most upregulated lncRNA in cancer tissues and significantly correlated with the metastasis of prostate cancer.…”

Circular RNA hsa_circ_0000567 can be used as a promising diagnostic biomarker for human colorectal cancer

“…Therefore, exploring the molecular mechanism underlying CRC carcinogenesis and metastasis may provide novel insight into CRC diagnosis and therapy. As is known, ncRNAs, such as miRNAs, lncRNAs are involved in the development and progression of CRC . However, as a novel identified ncRNAs, the relationship between circRNAs and CRC development is still unknown …”

A Practical Approach to Tumor Heterogeneity in Clinical Research and Diagnostics

“…The increasing evidence of the important role of micro-RNA and long noncoding RNAs in coding gene expression confirms their functional importance [41].…”