Abstract
Colorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.
Highlights
Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related death worldwide [1]
We identified nearly 200 papers by using the terms “circRNAs and colorectal cancer” while searching PubMed and Web of Science, sought out similar articles in PubMed, and checked the cited literature in the references until August 2020
Clinical significance of circRNAs in colorectal cancer (CRC) Compared with other noncoding RNAs (ncRNAs), such as miRNAs and long noncoding RNAs (lncRNAs), circRNAs are more suitable as diagnostic and prognostic biomarkers because of their high stability, long half-life (> 48 h), tissue-specific expression, and unique expression signatures, which are significantly associated with cancer progression and outcomes
Summary
Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related death worldwide [1]. Oncogenic functions Generally, upregulated circRNAs function as oncogenes in CRC and promote cell proliferation, migration and invasion but inhibit cell cycle arrest and apoptosis (Fig. 3a, b and d; Additional file 2). Geng et al confirmed that the overexpression of hsa_circ_0009361 suppresses the proliferation, EMT, migration, and invasion of CRC cells by upregulating the expression of APC2 and inhibiting the activity of the Wnt/β-catenin pathway, which is capable of inducing EMT [73].
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