Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

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.

Structures and target RNA preferences of the RNA-binding protein family of IGF2BPs: An overview

“…Despite their identification as binders to the name-giving 5 0 -UTR (untranslated region) of IGFII mRNA, the majority of targeted sequences maps to 3 0 -UTRs, while strongly regulated mRNAs like MYC comprise distinct binding sites in their coding regions. Figure 1A samples representative target mRNAs and additional RNAs bound by IMPs and summarized in the literature (Bell et al, 2013;Degrauwe et al, 2016;Lederer et al, 2014;Long et al, 2021).…”

Circular RNAs in Hepatocellular Carcinoma: Emerging Functions to Clinical Significances

“…Therefore, upregulated expression of these circRNAs in HCC may have oncogenic roles, and silencing expression of these circRNAs have opposite effects in HCC. Small-interfering RNAs that are designed to target the backsplicing junction sites of oncogenic circRNAs can inhibit the development of HCC and exhibit an antitumor effect (141,142). Some circRNAs with downregulated expression act as tumor suppressors and inhibit HCC development, also making them potential therapeutic targets.…”

Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

“…They can be detected not only in tissue biopsy from CRC patients, but also in a liquid one. Based on the literature review, there are many studies that indicate dysregulated circRNAs in CRC tissues and cells, in blood from CRC patients, in secreted from various cells exosomes [ 11 , 12 , 13 , 14 , 15 ]. Moreover, their oncogenic function is explained by a different mechanism like miRNA sponging, sponging or enhancing protein function, peptide translation, cancer-related signaling pathway regulation [ 11 , 16 ].…”