Skip to main content

Advertisement

Log in

Hsa_circ_0137652 Regulates miR-1205/CCNB1 Axis to Accelerate the Malignancy of Breast Cancer

  • Original Paper
  • Published:
Molecular Biotechnology Aims and scope Submit manuscript

Abstract

CircRNAs have become a hotspot in tumor research owing to their high stability and specific functions. We investigated the function of hsa_circ_0137652 in the onset and progression of breast cancer (BC). The expression of circ_0137652, miR-1205, and CCNB1 in BC tissues and cell lines were detected using RT-qPCR and/or western blotting. Dual-luciferase reporter and RNA immunoprecipitation chip assays were used to confirm any potential connections between circ_0137652, miR-1205, and CCNB1. CCK-8 and clone formation assays (CFA) were used to measure the proliferation of BC cells. The Transwell assay was used to investigate the migration of BC cells, and the impact of circ_0137652 on BC tumor formation in vivo was validated using animal experiments. RT-qPCR results showed that circ_0137652 and CCNB1 in breast cancer tissues were notably upregulated in normal tissues, whereas miR-1205 was prominently downregulated. After silencing circ_0137652, the growth and migration of BC cells were reduced. Animal experiments showed that circ_0137652 hampers the tumorigenesis of BC cells in vivo. Additionally, we found that circ_0137652 functions as a sponge for miR-1205. Moreover, the miR-1205 inhibitor notably facilitated cell proliferation and migration and attenuated the action of circ_0137652 knockdown. Furthermore, miR-1205 inhibits BC progression by targeting CCNB1. Circ_0137652 controls the miR-1205/CCNB1 axis to induce increased breast cancer malignancy. Our findings suggest that circ_0137652 may be a novel target for BC therapy.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

This article contains all of the data that were created or examined during this investigation.

References

  1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209–249.

    PubMed  Google Scholar 

  2. Cao, W., Chen, H. D., Yu, Y. W., Li, N., & Chen, W. Q. (2021). Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chinese Medical Journal (England), 134, 783–791.

    Article  Google Scholar 

  3. Shien, T., & Iwata, H. (2020). Adjuvant and neoadjuvant therapy for breast cancer. Japanese Journal of Clinical Oncology, 50, 225–229.

    Article  PubMed  Google Scholar 

  4. Giaquinto, A. N., Sung, H., Miller, K. D., Kramer, J. L., Newman, L. A., Minihan, A., Jemal, A., & Siegel, R. L. (2022). Breast Cancer Statistics, 2022. CA: A Cancer Journal for Clinicians, 72, 524–541.

    PubMed  Google Scholar 

  5. Kristensen, L. S., Andersen, M. S., Stagsted, L. V. W., Ebbesen, K. K., Hansen, T. B., & Kjems, J. (2019). The biogenesis, biology and characterization of circular RNAs. Nature Reviews. Genetics, 20, 675–691.

    Article  CAS  PubMed  Google Scholar 

  6. Chen, L., Wang, C., Sun, H., Wang, J., Liang, Y., Wang, Y., & Wong, G. (2021). The bioinformatics toolbox for circRNA discovery and analysis. Briefings in Bioinformatics, 22, 1706–1728.

    Article  CAS  PubMed  Google Scholar 

  7. Li, J., Sun, D., Pu, W., Wang, J., & Peng, Y. (2020). Circular RNAs in cancer: Biogenesis, function, and clinical significance. Trends Cancer, 6, 319–336.

    Article  CAS  PubMed  Google Scholar 

  8. Tang, L., Jiang, B., Zhu, H., Gao, T., Zhou, Y., Gong, F., He, R., Xie, L., & Li, Y. (2021). The biogenesis and functions of circRNAs and their roles in breast cancer. Frontiers in Oncology, 11, 605988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sang, Y., Chen, B., Song, X., Li, Y., Liang, Y., Han, D., Zhang, N., Zhang, H., Liu, Y., Chen, T., Li, C., Wang, L., Zhao, W., & Yang, Q. (2019). circRNA_0025202 regulates tamoxifen sensitivity and tumor progression via regulating the miR-182-5p/FOXO3a axis in breast cancer. Molecular Therapy: The Journal of the American Society of Gene Therapy, 27, 1638–1652.

    Article  CAS  PubMed  Google Scholar 

  10. Zheng, X., Huang, M., Xing, L., Yang, R., Wang, X., Jiang, R., Zhang, L., & Chen, J. (2020). The circRNA circSEPT9 mediated by E2F1 and EIF4A3 facilitates the carcinogenesis and development of triple-negative breast cancer. Molecular Cancer, 19, 73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Du, W. W., Yang, W., Li, X., Awan, F. M., Yang, Z., Fang, L., Lyu, J., Li, F., Peng, C., Krylov, S. N., Xie, Y., Zhang, Y., He, C., Wu, N., Zhang, C., Sdiri, M., Dong, J., Ma, J., Gao, C., … Yang, B. B. (2018). A circular RNA circ-DNMT1 enhances breast cancer progression by activating autophagy. Oncogene, 37, 5829–5842.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang, M., Bai, X., Zeng, X., Liu, J., Liu, F., & Zhang, Z. (2021). circRNA-miRNA-mRNA in breast cancer. Clinica Chimica Acta, 523, 120–130.

    Article  CAS  Google Scholar 

  13. Panda, A. C. (2018). Circular RNAs act as miRNA sponges. Advances in Experimental Medicine and Biology, 1087, 67–79.

    Article  CAS  PubMed  Google Scholar 

  14. Ferragut Cardoso, A. P., Udoh, K. T., & States, J. C. (2020). Arsenic-induced changes in miRNA expression in cancer and other diseases. Toxicology and Applied Pharmacology, 409, 115306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu, Z., Zhou, Y., Liang, G., Ling, Y., Tan, W., Tan, L., Andrews, R., Zhong, W., Zhang, X., Song, E., & Gong, C. (2019). Circular RNA hsa_circ_001783 regulates breast cancer progression via sponging miR-200c-3p. Cell Death & Disease, 10, 55.

    Article  Google Scholar 

  16. Wang, W. B., Ren, P., Ren, F. H., Huang, M., & Cheng, X. (2021). Circ_0000526 blocks the progression of breast cancer by sponging miR-492. Cancer Biotherapy & Radiopharmaceuticals, 36, 467–476.

    Article  CAS  Google Scholar 

  17. Su, N., Liu, L., He, S., & Zeng, L. (2021). Circ_0001666 affects miR-620/WNK2 axis to inhibit breast cancer progression. Genes Genomics, 43, 947–959.

    Article  CAS  PubMed  Google Scholar 

  18. Wang, J., Li, T., & Wang, B. (2021). Circ-UBAP2 functions as sponges of miR-1205 and miR-382 to promote glioma progression by modulating STC1 expression. Cancer Medicine, 10, 1815–1828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wu, Z., Shi, W., & Jiang, C. (2018). Overexpressing circular RNA hsa_circ_0002052 impairs osteosarcoma progression via inhibiting Wnt/β-catenin pathway by regulating miR-1205/APC2 axis. Biochemical and Biophysical Research Communications, 502, 465–471.

    Article  CAS  PubMed  Google Scholar 

  20. Zhong, W., Bao, L., Yuan, Y., & Meng, Y. (2021). CircRASSF2 acts as a prognostic factor and promotes breast cancer progression by modulating miR-1205/HOXA1 axis. Bioengineered, 12, 3014–3028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yin, Y., Zhang, J., Ma, T., Chen, D., & Lu, D. (2022). miR-1205/DNAJB1 reverses docetaxel chemoresistance in human triple negative breast carcinoma cells via regulation of mutp53/TAp63 signaling. Acta Biochimica et Biophysica Sinica, 54, 37–46.

    Article  CAS  PubMed  Google Scholar 

  22. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402–408.

    Article  CAS  PubMed  Google Scholar 

  23. Cao, L., Wang, M., Dong, Y., Xu, B., Chen, J., Ding, Y., Qiu, S., Li, L., Karamfilova Zaharieva, E., Zhou, X., & Xu, Y. (2020). Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2. Cell Death & Disease, 11, 145.

    Article  CAS  Google Scholar 

  24. Kristensen, L. S., Jakobsen, T., Hager, H., & Kjems, J. (2022). The emerging roles of circRNAs in cancer and oncology. Nature Reviews. Clinical Oncology, 19, 188–206.

    Article  CAS  PubMed  Google Scholar 

  25. Chen, J., Gu, J., Tang, M., Liao, Z., Tang, R., Zhou, L., Su, M., Jiang, J., Hu, Y., Chen, Y., Zhou, Y., Liao, Q., Xiong, W., Zhou, J., Tang, Y., & Nie, S. (2022). Regulation of cancer progression by circRNA and functional proteins. Journal of Cellular Physiology, 237, 373–388.

    Article  CAS  PubMed  Google Scholar 

  26. Wu, Z., Yu, X., Zhang, S., He, Y., & Guo, W. (2022). Mechanism underlying circRNA dysregulation in the TME of digestive system cancer. Frontiers in Immunology, 13, 951561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zeng, K., He, B., Yang, B. B., Xu, T., Chen, X., Xu, M., Liu, X., Sun, H., Pan, Y., & Wang, S. (2018). The pro-metastasis effect of circANKS1B in breast cancer. Molecular Cancer, 17, 160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang, F., Wang, X., Li, J., Lv, P., Han, M., Li, L., Chen, Z., Dong, L., Wang, N., & Gu, Y. (2021). CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling. Journal of Biomedical Science, 28, 4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wan, L., Han, Q., Zhu, B., Kong, Z., & Feng, E. (2022). Circ-TFF1 facilitates breast cancer development via regulation of miR-338-3p/FGFR1 Axis. Biochemical Genetics, 60, 315–335.

    Article  CAS  PubMed  Google Scholar 

  30. Takizawa, C. G., & Morgan, D. O. (2000). Control of mitosis by changes in the subcellular location of cyclin-B1-Cdk1 and Cdc25C. Current Opinion in Cell Biology, 12, 658–665.

    Article  CAS  PubMed  Google Scholar 

  31. Bao, B., Yu, X., & Zheng, W. (2022). MiR-139-5p targeting CCNB1 modulates proliferation, migration, invasion and cell cycle in lung adenocarcinoma. Molecular Biotechnology, 64, 852–860.

    Article  CAS  PubMed  Google Scholar 

  32. Zou, Y., Ruan, S., Jin, L., Chen, Z., Han, H., Zhang, Y., Jian, Z., Lin, Y., Shi, N., & Jin, H. (2020). CDK1, CCNB1, and CCNB2 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma. Medical Science Monitor, 26, e925289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li, S., Liu, N., Piao, J., Meng, F., & Li, Y. (2020). CCNB1 expedites the progression of cervical squamous cell carcinoma via the regulation by FOXM1. Oncotargets and Therapy, 13, 12383–12395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lu, Y., Yang, G., Xiao, Y., Zhang, T., Su, F., Chang, R., Ling, X., & Bai, Y. (2020). Upregulated cyclins may be novel genes for triple-negative breast cancer based on bioinformatic analysis. Breast Cancer, 27, 903–911.

    Article  PubMed  Google Scholar 

  35. Androic, I., Krämer, A., Yan, R., Rödel, F., Gätje, R., Kaufmann, M., Strebhardt, K., & Yuan, J. (2008). Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol. BMC Cancer, 8, 391.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zhang, H., Zhang, X., Li, X., Meng, W. B., Bai, Z. T., Rui, S. Z., Wang, Z. F., Zhou, W. C., & Jin, X. D. (2018). Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer. Journal of Cellular Physiology, 234, 619–631.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

This work was supported by the Youth Project of the Wuhan Municipal Health Commission under the project name “Efficacy and safety of percutaneous acupoint electrical stimulation based on ‘Biaoben acupoints combination’ in the treatment of breast cancer-related fatigue.” (Project Number: S202204110000), [Grant number: WZ22Q18].

Author information

Authors and Affiliations

Authors

Contributions

Both the experiments and the data analysis were done by XZ and QZ. MX conceptualized and created the study. XZ and MX gathered the data. QZ and MX were in charge of data analysis and interpretation. The paper was written by XZ and QZ. The manuscript was reviewed and revised by MX. All authors evaluated and approved the article.

Corresponding author

Correspondence to Min Xiao.

Ethics declarations

Conflict of interest

According to the authors, there were no conflicts of interest.

Ethical Approval

This study was authorized by the medical ethics committee of the Wuhan Red Cross Hospital (Wuhan, China). The Declaration of Helsinki's ethical guidelines were followed in the processing of the clinical tissue samples. A form for informed consent was filled out by each patient. All of the patients completed an informed consent form. The animal experiment conducted observed the ARRIVE guidelines and was authorized by the Animal Care and Use Committee of Wuhan Red Cross Hospital (Wuhan, China).

Consent to Participate

Each patient completed an informed consent form in writing.

Consent for Publication

The participants gave their consent for the study to be published.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, X., Zhao, Q. & Xiao, M. Hsa_circ_0137652 Regulates miR-1205/CCNB1 Axis to Accelerate the Malignancy of Breast Cancer. Mol Biotechnol 65, 1824–1835 (2023). https://doi.org/10.1007/s12033-023-00684-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12033-023-00684-4

Keywords

Navigation