Skip to main content

Advertisement

SpringerLink
Log in

CircRNAs: promising factors for regulating angiogenesis in colorectal cancer

  • Review Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Colorectal cancer (CRC) is one of the most common cancers in the world. The incidence rate of cancer is high. The overall response to traditional treatment methods such as surgery, radiotherapy, and chemotherapy is not very satisfactory. Therefore, finding new therapeutic targets is very important for improving CRC treatment. In recent reports, the role of circRNAs in regulating colorectal angiogenesis has been gradually revealed. CircRNAs can indirectly act on angiogenesis pathways and regulate the expression of growth factors such as vascular endothelial growth factor (VEGF). CircRNAs are endogenous noncoding RNAs formed by pre-mRNAs through exon circular splicing. The covalent closed-loop structure makes these RNAs highly conserved and stable. CircRNAs have been found in human plasma, serum, urine, and other body fluids. Their highly conserved characteristics play important roles in many biological activities. CircRNAs can participate in the progression of many diseases by sponging miRNAs, interacting with proteins, and regulating transcription. Angiogenesis can provide nutrients and oxygen for tumour proliferation and metastasis. Angiogenesis is an important sign of the formation of the tumour microenvironment. Here, we will summarize the role of the latest circRNAs in the mechanism of angiogenesis in CRC and provide potential therapeutic targets for clinical treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and materials

Not applicable.

References

  1. Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

    PubMed  Google Scholar 

  2. Siegel RL, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.

    Article  PubMed  Google Scholar 

  3. Sung JJ, et al. Asia Pacific consensus recommendations for colorectal cancer screening. Gut. 2008;57(8):1166–76.

    Article  CAS  PubMed  Google Scholar 

  4. Dekker E, et al. Colorectal cancer. Lancet. 2019;394(10207):1467–80.

    Article  PubMed  Google Scholar 

  5. Tang Y, et al. MicroRNAs and angiogenesis: a new era for the management of colorectal cancer. Cancer Cell Int. 2021;21(1):221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Seymour MT, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007;370(9582):143–52.

    Article  CAS  PubMed  Google Scholar 

  7. Marisi G, et al. Circulating VEGF and eNOS variations as predictors of outcome in metastatic colorectal cancer patients receiving bevacizumab. Sci Rep. 2017;7(1):1293.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407(6801):249–57.

    Article  CAS  PubMed  Google Scholar 

  9. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov. 2011;10(6):417–27.

    Article  CAS  PubMed  Google Scholar 

  10. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  11. Chen C, et al. The circular RNA 001971/miR-29c-3p axis modulates colorectal cancer growth, metastasis, and angiogenesis through VEGFA. J Exp Clin Cancer Res. 2020;39(1):91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668–81.

    Article  CAS  PubMed  Google Scholar 

  13. Viallard C, Larrivée B. Tumor angiogenesis and vascular normalization: alternative therapeutic targets. Angiogenesis. 2017;20(4):409–26.

    Article  CAS  PubMed  Google Scholar 

  14. Bagnasco L, et al. Role of angiogenesis inhibitors in colorectal cancer: sensitive and insensitive tumors. Curr Cancer Drug Targets. 2012;12(4):303–15.

    Article  CAS  PubMed  Google Scholar 

  15. Widakowich C, et al. Review: side effects of approved molecular targeted therapies in solid cancers. Oncologist. 2007;12(12):1443–55.

    Article  CAS  PubMed  Google Scholar 

  16. Dai J, et al. CircRNA UBAP2 facilitates the progression of colorectal cancer by regulating miR-199a/VEGFA pathway. Eur Rev Med Pharmacol Sci. 2020;24(15):7963–71.

    CAS  PubMed  Google Scholar 

  17. Hsu MT, Coca-Prados M. Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature. 1979;280(5720):339–40.

    Article  CAS  PubMed  Google Scholar 

  18. Ashwal-Fluss R, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56(1):55–66.

    Article  CAS  PubMed  Google Scholar 

  19. Chen LL. The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016;17(4):205–11.

    Article  CAS  PubMed  Google Scholar 

  20. Liang D, Wilusz JE. Short intronic repeat sequences facilitate circular RNA production. Genes Dev. 2014;28(20):2233–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Jeck WR, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19(2):141–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li Z, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015;22(3):256–64.

    Article  PubMed  CAS  Google Scholar 

  23. Huang C, et al. A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs. Genes Dev. 2018;32(9–10):639–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ma Z, et al. circ5615 functions as a ceRNA to promote colorectal cancer progression by upregulating TNKS. Cell Death Dis. 2020;11(5):356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hansen TB, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–8.

    Article  CAS  PubMed  Google Scholar 

  26. Abdelmohsen K, et al. Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol. 2017;14(3):361–9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Li A, et al. Circular RNA in colorectal cancer. J Cell Mol Med. 2021;25(8):3667–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pamudurti NR, et al. Translation of CircRNAs. Mol Cell. 2017;66(1):9-21.e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bak RO, Mikkelsen JG. miRNA sponges: soaking up miRNAs for regulation of gene expression. Wiley Interdiscip Rev RNA. 2014;5(3):317–33.

    Article  CAS  PubMed  Google Scholar 

  30. Shang A, et al. Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis. Mol Cancer. 2020;19(1):117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhao X, Cai Y, Xu J. Circular RNAs: biogenesis, mechanism, and function in human cancers. Int J Mol Sci. 2019;20(16):3926.

    Article  CAS  PubMed Central  Google Scholar 

  32. Yang H, et al. CircPTK2 (hsa_circ_0005273) as a novel therapeutic target for metastatic colorectal cancer. Mol Cancer. 2020;19(1):13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Han K, et al. CircLONP2 enhances colorectal carcinoma invasion and metastasis through modulating the maturation and exosomal dissemination of microRNA-17. Mol Cancer. 2020;19(1):60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zheng X, et al. A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling. Mol Cancer. 2019;18(1):47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Pan Z, et al. A novel protein encoded by circFNDC3B inhibits tumor progression and EMT through regulating Snail in colon cancer. Mol Cancer. 2020;19(1):71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen LY, et al. The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1α translation. Mol Cancer. 2020;19(1):164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 2003;9(6):677–84.

    Article  CAS  PubMed  Google Scholar 

  38. Gilkes DM, Semenza GL, Wirtz D. Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer. 2014;14(6):430–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Carmeliet P, et al. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature. 1998;394(6692):485–90.

    Article  CAS  PubMed  Google Scholar 

  40. Braunstein S, et al. A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer. Mol Cell. 2007;28(3):501–12.

    Article  CAS  PubMed  Google Scholar 

  41. Guo Y, et al. Circ3823 contributes to growth, metastasis and angiogenesis of colorectal cancer: involvement of miR-30c-5p/TCF7 axis. Mol Cancer. 2021;20(1):93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chen H, Liu H, Qing G. Targeting oncogenic Myc as a strategy for cancer treatment. Signal Transduct Target Ther. 2018;3:5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Wu SY, Lan SH, Liu HS. Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis. Autophagy. 2019;15(4):729–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ramos-García P, et al. An update on the implications of cyclin D1 in oral carcinogenesis. Oral Dis. 2017;23(7):897–912.

    Article  PubMed  Google Scholar 

  45. Pantel K, Alix-Panabières C. Circulating tumour cells in cancer patients: challenges and perspectives. Trends Mol Med. 2010;16(9):398–406.

    Article  PubMed  Google Scholar 

  46. Bachmayr-Heyda A, et al. Correlation of circular RNA abundance with proliferation–exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues. Sci Rep. 2015;5:8057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Takahashi Y, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995;55(18):3964–8.

    CAS  PubMed  Google Scholar 

  48. Grothey A, Galanis E. Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol. 2009;6(9):507–18.

    Article  CAS  PubMed  Google Scholar 

  49. Jiang Z, et al. EIF4A3-induced circ_0084615 contributes to the progression of colorectal cancer via miR-599/ONECUT2 pathway. J Exp Clin Cancer Res. 2021;40(1):227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang X, et al. MicroRNA-599 inhibits metastasis and epithelial-mesenchymal transition via targeting EIF5A2 in gastric cancer. Biomed Pharmacother. 2018;97:473–80.

    Article  CAS  PubMed  Google Scholar 

  51. Wang DP, et al. microRNA-599 promotes apoptosis and represses proliferation and epithelial-mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2-depentent Notch signaling pathway. J Cell Physiol. 2020;235(3):2492–505.

    Article  CAS  PubMed  Google Scholar 

  52. Sun Y, et al. MiR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma. Mol Cell Biochem. 2014;390(1–2):19–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Qi JH, et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med. 2003;9(4):407–15.

    Article  CAS  PubMed  Google Scholar 

  54. Zeng W, et al. CircFNDC3B sequestrates miR-937-5p to derepress TIMP3 and inhibit colorectal cancer progression. Mol Oncol. 2020;14(11):2960–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Jin L, et al. Circ_0030998 promotes tumor proliferation and angiogenesis by sponging miR-567 to regulate VEGFA in colorectal cancer. Cell Death Discov. 2021;7(1):160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zheng X, et al. Circ_0056618 promoted cell proliferation, migration and angiogenesis through sponging with miR-206 and upregulating CXCR4 and VEGF-A in colorectal cancer. Eur Rev Med Pharmacol Sci. 2020;24(8):4190–202.

    CAS  PubMed  Google Scholar 

  57. Wu G, et al. Circ-RNF111 aggravates the malignancy of gastric cancer through miR-876-3p-dependent regulation of KLF12. World J Surg Oncol. 2021;19(1):259.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Kim SH, et al. Krüppel-like factor 12 promotes colorectal cancer growth through early growth response protein 1. PLoS ONE. 2016;11(7): e0159899.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Bai L, et al. Circular noncoding RNA circ_0007334 sequestrates miR-577 to derepress KLF12 and accelerate colorectal cancer progression. Anticancer Drugs. 2022;33(1):e409–22.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Chinese Foundation for Hepatitis Prevention and Control—‘Tian-qing-gan-bing’ Research Fund, No. TQGB20190165; College Students’ Innovation, Entrepreneurship and Excellence Program of Lanzhou University in 2022 (20220060024).

Author information

Author notes

  1. Xiaohu Guo and Xingyu Chang have contributed equally to this study and share first authorship.

Authors and Affiliations

  1. General Surgery Department, The Second Hospital of Lanzhou University, Lanzhou, 730030, China

    Xiaohu Guo, Zheyuan Wang & Zhengang Wei

  2. The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, Gansu, China

    Xingyu Chang & Chenjun Jiang

Authors
  1. Xiaohu Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xingyu Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zheyuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chenjun Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhengang Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, XG; Methodology, XC; Software, ZW; revised version of manuscript, CJ; Validation, ZW. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Zhengang Wei.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, X., Chang, X., Wang, Z. et al. CircRNAs: promising factors for regulating angiogenesis in colorectal cancer. Clin Transl Oncol 24, 1673–1681 (2022). https://doi.org/10.1007/s12094-022-02829-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-022-02829-4

Keywords

Search

Navigation