Skip to main content

Advertisement

Log in

Overexpression of Long Non-coding RNA uc.246 Facilitates Angiogenesis, Migration, and EMT Phenotype of Human Breast Cancer Cells

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Breast cancer is the most malignant subtype of gynecological tumors and with aggressive biological behavior and poor outcome. Ultra-conserved non-coding RNA (ucRNA) is a newly discovered class of long non-coding RNAs (lncRNAs) which involved in the regulation of interaction network of genes. However, the exact function and mechanism by which ucRNA modulates breast cancer aggressive has not yet to be completely elucidated. In the present study, we demonstrated that the expression of uc.246 was significantly upregulated in metastatic breast cancer patients and TNBC cell lines, compared with those in controls. Furthermore, overexpression of uc.246 in MCF-7 cell lines enhanced the capacity of breast cancer cells to induce tube formation and migration of HUVECs, and, finally, enhanced breast cancer cells metastasis. Meanwhile, uc.246 overexpressing enhances the EMT phenotype of TNBC cells. Mechanistically, we found that uc.246 promoted malignant progression of breast cancer via upregulating the levels of VEGF-C and increased the levels of mesenchymal marker protein. Our results demonstrated that uc.246 induced angiogenesis, migration, and EMT phenotype and may represent a novel prognostic biomarker and therapeutic target for patients with breast cancer.

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

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.

References

  1. Sung, H., Ferlay, J., Siegel, R. L., et al. (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. Soerjomataram, I., & Bray, F. (2021). Planning for tomorrow: Global cancer incidence and the role of prevention 2020–2070. Nature Reviews Clinical Oncology, 18, 663–672.

    Article  PubMed  Google Scholar 

  3. Elston, C. W., Ellis, I. O., & Pinder, S. E. (1999). Pathological prognostic factors in breast cancer. Critical Reviews in Oncology/Hematology, 31, 209–223.

    Article  CAS  PubMed  Google Scholar 

  4. Hill, D. A., Friend, S., Lomo, L., et al. (2018). Breast cancer survival, survival disparities, and guideline-based treatment. Breast Cancer Research and Treatment, 170, 405–414.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Raica, M., Jitariu, A. A., & Cimpean, A. M. (2016). Lymphangiogenesis and anti-lymphangiogenesis in cutaneous melanoma. Anticancer Research, 36, 4427–4435.

    Article  CAS  PubMed  Google Scholar 

  6. Al-Rawi, M. A., & Jiang, W. G. (2011). Lymphangiogenesis and cancer metastasis. Frontiers in Bioscience, 16, 723–739.

    Article  CAS  Google Scholar 

  7. Alitalo, K., Tammela, T., & Petrova, T. V. (2005). Lymphangiogenesis in development and human disease. Nature, 438, 946–953.

    Article  CAS  PubMed  ADS  Google Scholar 

  8. Mariotti, V., Fiorotto, R., Cadamuro, M., et al. (2021). New insights on the role of vascular endothelial growth factor in biliary pathophysiology. JHEP Reports: Innovation in Hepatology, 3, 100251.

    Article  PubMed  Google Scholar 

  9. McColl, B. K., Stacker, S. A., & Achen, M. G. (2004). Molecular regulation of the VEGF family – Inducers of angiogenesis and lymphangiogenesis. APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica, 112, 463–480.

    Article  CAS  PubMed  Google Scholar 

  10. Hu, X., & Luo, J. (2018). Heterogeneity of tumor lymphangiogenesis: Progress and prospects. Cancer Science, 109, 3005–3012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Song, E., Mao, T., Dong, H., et al. (2020). VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature, 577, 689–694.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  12. Li, W. N., Hsiao, K. Y., Wang, C. A., et al. (2020). Extracellular vesicle-associated VEGF-C promotes lymphangiogenesis and immune cells infiltration in endometriosis. Proceedings of the National Academy of Sciences of the United States of America, 117, 25859–25868.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  13. Karaman, S., & Detmar, M. (2014). Mechanisms of lymphatic metastasis. The Journal of Clinical Investigation, 124, 922–928.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dieterich, L. C., & Detmar, M. (2016). Tumor lymphangiogenesis and new drug development. Advanced Drug Delivery Reviews, 99, 148–160.

    Article  CAS  PubMed  Google Scholar 

  15. Mittal, V. (2018). Epithelial mesenchymal transition in tumor metastasis. Annual Review of Pathology, 13, 395–412.

    Article  CAS  PubMed  Google Scholar 

  16. Zhang, Y., & Weinberg, R. A. (2018). Epithelial-to-mesenchymal transition in cancer: Complexity and opportunities. Frontiers of Medicine, 12, 361–373.

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  17. Chen, T., You, Y., Jiang, H., et al. (2017). Epithelial-mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. Journal of Cellular Physiology, 232, 3261–3272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Esteller, M. (2011). Non-coding RNAs in human disease. Nature Reviews Genetics, 12, 861–874.

    Article  CAS  PubMed  Google Scholar 

  19. Liz, J., Portela, A., Soler, M., et al. (2014). Regulation of pri-miRNA processing by a long noncoding RNA transcribed from an ultraconserved region. Molecular Cell, 55, 138–147.

    Article  CAS  PubMed  Google Scholar 

  20. Terracciano, D., Terreri, S., de Nigris, F., et al. (2017). The role of a new class of long noncoding RNAs transcribed from ultraconserved regions in cancer. Biochimica et Biophysica Acta Reviews on Cancer, 1868, 449–455.

    Article  CAS  PubMed  Google Scholar 

  21. Bejerano, G., Pheasant, M., Makunin, I., et al. (2004). Ultraconserved elements in the human genome. Science, 304, 1321–1325.

    Article  CAS  PubMed  ADS  Google Scholar 

  22. Zhou, J., Wang, R., Zhang, J., et al. (2017). Conserved expression of ultra-conserved noncoding RNA in mammalian nervous system. Biochimica et Biophysica Acta Gene Regulatory Mechanisms, 1860, 1159–1168.

    Article  CAS  PubMed  Google Scholar 

  23. Jiang, B. C., Yang, T., He, L. N., et al. (2016). Altered T-UCRs expression profile in the spinal cord of mice with neuropathic pain. Translational Perioperative and Pain Medicine, 1, 1–10.

    PubMed  PubMed Central  Google Scholar 

  24. Kopp, F., & Mendell, J. T. (2018). Functional classification and experimental dissection of long noncoding RNAs. Cell, 172, 393–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wilusz, J. E., Sunwoo, H., & Spector, D. L. (2009). Long noncoding RNAs: Functional surprises from the RNA world. Genes & Development, 23, 1494–1504.

    Article  CAS  Google Scholar 

  26. Hombach, S., & Kretz, M. (2016). Non-coding RNAs: Classification, biology and functioning. Advances in Experimental Medicine and Biology, 937, 3–17.

    Article  CAS  PubMed  Google Scholar 

  27. Malmuthuge, N., & Guan, L. L. (2021). Noncoding RNAs: Regulatory molecules of host-microbiome crosstalk. Trends in Microbiology, 29, 713–724.

    Article  CAS  PubMed  Google Scholar 

  28. Zhang, Y., Mao, Q., Xia, Q., et al. (2021). Noncoding RNAs link metabolic reprogramming to immune microenvironment in cancers. Journal of Hematology & Oncology, 14, 169.

    Article  CAS  Google Scholar 

  29. Cunnick, G. H., Jiang, W. G., Gomez, K. F., et al. (2002). Lymphangiogenesis and breast cancer metastasis. Histology and Histopathology, 17, 863–870.

    CAS  PubMed  Google Scholar 

  30. Roy, S., Banerjee, P., Ekser, B., et al. (2021). Targeting lymphangiogenesis and lymph node metastasis in liver cancer. The American Journal of Pathology, 191, 2052–2063.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sammarco, G., Varricchi, G., Ferraro, V., et al. (2019). Mast cells, angiogenesis and lymphangiogenesis in human gastric cancer. International Journal of Molecular Sciences, 20(9), 2106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This work was in part supported by grants from the Natural Science Foundation of China (No.82003116).

Author information

Authors and Affiliations

Authors

Contributions

YL and XPH were performed experiments, analysis and interpretation of data, YL and WFX design and wrote manuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to Wenfei Xia.

Ethics declarations

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no known competing financial interests.

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

Liu, Y., Hu, X. & Xia, W. Overexpression of Long Non-coding RNA uc.246 Facilitates Angiogenesis, Migration, and EMT Phenotype of Human Breast Cancer Cells. Appl Biochem Biotechnol 196, 1142–1153 (2024). https://doi.org/10.1007/s12010-023-04572-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-023-04572-0

Keywords

Navigation