Expression profiles of circular RNAs in human colorectal cancer based on RNA deep sequencing

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.

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“…Additional file 1. Expression profiling of circRNAs in colorectal cancer [212][213][214][215][216][217][218][219][220][221][222][223].…”

Section: Supplementary Informationmentioning

confidence: 99%

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

et al. 2021

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“…Circular RNAs (circRNAs) are competitive endogenous RNAs which modulate gene expression and biological function via miRNA sponging (21,22). CircRNAs are highly expressed in multiple tumor tissues, including CRC (23,24). CircRNAs participate in cancer-associated physiological and pathological processes, such as cell proliferation, migration and invasion, cell cycle progression, metastasis and carcinogenesis (25).…”

Section: Introductionmentioning

confidence: 99%

Hsa_circ_0038646 promotes cell proliferation and migration in colorectal cancer via miR‑331‑3p/GRIK3

Zhou

Chen

et al. 2020

Oncol Lett

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Increasing evidence supports the essential roles of circular RNAs (circRNAs) and microRNAs (miRNAs/miRs) in different types of human cancer. For example, hsa_ circ_0137008 functions as a sponge for mi-338-5p and inhibits the malignant phenotype in colorectal cancer. Furthermore, hsa_circ_RNA_0011780 downregulates FBXW7 by targeting miR-554a and suppressing the progression of non-small cell lung cancer. Thus far, only a single report has identified that the miRNA miR-331-3p exerts a pivotal effect on human colorectal cancer (CRC) evolution. However, both the upand downstream regulatory mechanisms of miR-331-3p are unclear. In the present study, it was predicted via bioinformatics analysis that the circRNA, hsa_circ_0038646, and the glutamate receptor ionotropic kainate 3 (GRIK3) gene contain binding sites that can interact with miR-331-3p. Thus, hsa_ circ_0038646/miR-331-3p/GRIK3 may be a novel therapeutic pathway for CRC. Reverse transcription-quantitative PCR and western blotting analyses were performed, as well as cell proliferation, luciferase reporter and Transwell migration assays. Hsa_circ_0038646 was overexpressed in both CRC cells and tissues, and this aberrant expression was positively related with increasing tumor grade. Knockdown of hsa_circ_0038646 significantly weakened human CRC cell proliferation and migration. It was shown that hsa_circ_0038646 can sponge miR-331-3p to suppress its expression, and that suppression of miR-331-3p can reverse the effects of hsa_circ_0038646 inhibition in CRC cells. It was determined that GRIK3 is a downstream target of miR-331-3p, and that hsa_circ_0038646 could increase the levels of GRIK3 by suppressing miR-331-3p in CRC cells. Restoring GRIK3 expression rescued the weakened CRC cell proliferation and migration following hsa_circ_0038646 knockdown. The present study indicated that hsa_circ_0038646 functions as a tumor promoter in CRC by increasing GRIK3 expression via sponging of miR-331-3p. The hsa_circ_0038646/miR-331-3p/GRIK3 axis may be a novel therapeutic and diagnostic target of CRC.

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“…More importantly, accumulating studies provided evidence that circRNAs become potentially stable biomarkers for the early precision diagnosis and therapeutic targets for CRC due to their higher stability, expression abundance, and regulatory function networks 28 . For example, hsa_circ_0000567 and hsa_circ_0142527 have been found to be a potential diagnosis biomarkers in CRC 29,30 . And circPPP1R12A can encode a 73aa peptide named as circPPP1R12A‐73aa and thus promote the pathogenesis and metastasis of CRC 31 .…”

Section: Discussionmentioning

confidence: 99%

“…28 For example, hsa_circ_0000567 and hsa_circ_0142527 have been found to be a potential diagnosis biomarkers in CRC. 29,30 And circPPP1R12A can encode a 73aa peptide named as circPPP1R12A-73aa and thus promote the pathogenesis and metastasis of CRC. 31 However, the function of most of the dysregulated circRNAs in CRC remains elusive.…”

Section: Discovering Of Bioactive Compounds For the Therapy Of Crcmentioning

confidence: 99%

Identification of functional circRNA/miRNA/mRNA regulatory network for exploring prospective therapy strategy of colorectal cancer

Wang

et al. 2020

J of Cellular Biochemistry

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Circular RNA (circRNA) has been reported to have great scientific significance and clinical value in multiple cancers including colorectal cancer (CRC). However, the biological function of most circRNAs in CRC is still in its infancy. Herein, we discovered the differential expressed circRNAs (DECs) between CRC tissues and matched adjacent using deep RNA sequencing and further confirmed the DECs expression by combining with another Gene Expression Omnibus dataset. Furthermore, we validated the expression of the top four upregulated circRNAs (hsa_circ_0030632, hsa_circ_0004887, hsa_circ_ 0001550, and hsa_circ_0001681) in both of paired CRC tissues and CRC cell lines. Then, a circRNA/microRNA/messenger RNA regulatory network was established and the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed these four circRNAs participated in various biological processed including apoptotic process and multiple metabolic processes. Moreover, based on the regulatory network, three bioactive compounds (pergolide, pivampicillin, and methylergometrine) for the treatment of CRC were also found. In conclusion, this study improved our understanding of circRNAs and may also facilitate the finding of promising targets and biomarkers in CRC.

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Expression profiles of circular RNAs in human colorectal cancer based on RNA deep sequencing

Cited by 18 publications

References 40 publications

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

Hsa_circ_0038646 promotes cell proliferation and migration in colorectal cancer via miR‑331‑3p/GRIK3

Identification of functional circRNA/miRNA/mRNA regulatory network for exploring prospective therapy strategy of colorectal cancer

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