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Review

Circular RNAs in colorectal cancer: From molecular mechanisms to therapeutic applications (Review)

  • Authors:
    • Yuxing He
    • Can Luo
    • Wei Du
    • Debei Liu
    • Lingshan Liao
    • Siqian Wang
    • Yanlin Cao
  • View Affiliations / Copyright

    Affiliations: Clinical Laboratory Department, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, Hunan 415000, P.R. China, Department of Pathology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, Hunan 415000, P.R. China
  • Article Number: 139
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    Published online on: August 11, 2025
       https://doi.org/10.3892/or.2025.8972
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Abstract

Circular RNAs (circRNAs) are stable, conserved non‑coding RNA molecules with key roles in gene regulation. Because of their tissue‑specific expression patterns and involvement in various cellular processes, circRNAs are relevant in cancer biology, specifically for colorectal cancer (CRC) diagnosis. The present review systematically examines the roles of circRNAs in CRC pathogenesis and their potential as diagnostic biomarkers and therapeutic targets for CRC, focusing on the key circRNAs involved in CRC development and progression, their molecular mechanisms and clinical value, as well as advances in circRNA‑based therapeutic strategies and challenges in the clinical translation of circRNA application.
View Figures

Figure 1

Biogenesis and key features of
circRNAs. Biogenesis of circRNAs involves back-splicing, exon
skipping, intron pairing and RNA-binding protein interactions. The
essential features of circRNAs included closed structure conferring
enhanced stability, distinct tissue specificity and translation
potential. These properties underlie the biological functions and
clinical applications of circRNAs. Created with Biorender. circ,
circular.

Figure 2

Molecular mechanisms and functions of
key circRNAs. Schematic illustration showing four major circRNA
regulatory pathways in cancer. Each pathway demonstrates a distinct
molecular mechanism (miRNA sponge, protein interaction,
transcriptional regulation and protein translation) and
representative circRNAs (CDR1-AS, circHIPK3, circPTK2 and
circPTEN1, respectively), which ultimately influence specific
cancer-related functions (PD-L1 regulation, cell proliferation,
metastasis and tumor suppression, respectively). Created with
Biorender. circ, circular.

Figure 3

Translational pathway of circRNA
research, involving integration of diagnostic characteristics
(stability, tissue specificity and disease association) with
therapeutic approaches (direct and mechanism-based targeting and
combined therapy). Technical strategies include RNA interference,
CRISPR editing, small molecule inhibitors and delivery systems,
leading to clinical trials with subsequent safety assessment for
future development. Created with Biorender. circ, circular; CRISPR
(Clustered Regularly interspaced Short Palindromic Repeats).

Figure 4

Bioinformatics resources for circRNA
research. Analysis tools enable network visualization (CircNetVis),
expression profiling (CircScan), differential analysis (EasyCircR)
and network prediction (CircNet 2.0). Database resources provide
sequence information (CircBase), interaction data
(CircInteractome), expression profiles (CircAtlas) and cancer
associations (CSCD). These resources support comprehensive
investigations on circRNAs from basic research to clinical
application. Created with Biorender. circ, circular; CSCD
(Cancer-Specific CircRNA Database).

Figure 5

Current challenges and future
perspectives in circRNA research. Technical, biological, and
clinical barriers indicate specific challenges, driving future
directions in delivery systems, targeting specificity,
mechanism-based research and standardization protocols. This
framework guides systematic improvement of circRNA-based
therapeutic approaches. Created with Biorender. circ, circular.
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Copy and paste a formatted citation
Spandidos Publications style
He Y, Luo C, Du W, Liu D, Liao L, Wang S and Cao Y: Circular RNAs in colorectal cancer: From molecular mechanisms to therapeutic applications (Review). Oncol Rep 54: 139, 2025.
APA
He, Y., Luo, C., Du, W., Liu, D., Liao, L., Wang, S., & Cao, Y. (2025). Circular RNAs in colorectal cancer: From molecular mechanisms to therapeutic applications (Review). Oncology Reports, 54, 139. https://doi.org/10.3892/or.2025.8972
MLA
He, Y., Luo, C., Du, W., Liu, D., Liao, L., Wang, S., Cao, Y."Circular RNAs in colorectal cancer: From molecular mechanisms to therapeutic applications (Review)". Oncology Reports 54.5 (2025): 139.
Chicago
He, Y., Luo, C., Du, W., Liu, D., Liao, L., Wang, S., Cao, Y."Circular RNAs in colorectal cancer: From molecular mechanisms to therapeutic applications (Review)". Oncology Reports 54, no. 5 (2025): 139. https://doi.org/10.3892/or.2025.8972
Copy and paste a formatted citation
x
Spandidos Publications style
He Y, Luo C, Du W, Liu D, Liao L, Wang S and Cao Y: Circular RNAs in colorectal cancer: From molecular mechanisms to therapeutic applications (Review). Oncol Rep 54: 139, 2025.
APA
He, Y., Luo, C., Du, W., Liu, D., Liao, L., Wang, S., & Cao, Y. (2025). Circular RNAs in colorectal cancer: From molecular mechanisms to therapeutic applications (Review). Oncology Reports, 54, 139. https://doi.org/10.3892/or.2025.8972
MLA
He, Y., Luo, C., Du, W., Liu, D., Liao, L., Wang, S., Cao, Y."Circular RNAs in colorectal cancer: From molecular mechanisms to therapeutic applications (Review)". Oncology Reports 54.5 (2025): 139.
Chicago
He, Y., Luo, C., Du, W., Liu, D., Liao, L., Wang, S., Cao, Y."Circular RNAs in colorectal cancer: From molecular mechanisms to therapeutic applications (Review)". Oncology Reports 54, no. 5 (2025): 139. https://doi.org/10.3892/or.2025.8972
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