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miR-497/195 Cluster Affects the Development of Colorectal Cancer by Targeting FRA1

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Abstract

The miR-497-195 cluster facilitates the occurrence and development of cancer. This study aims to investigate whether the miR-195-497 cluster could regulate the progression of colorectal cancer by regulating the common target gene, FOS-related antigen 1 (FRA1). Overexpression of the miR-195/497 vector was used to evaluate the effect of overexpression of miR-195-497 clusters on the biological behavior of colon cancer cells. In animal experiments, tumor growth and metastasis were recorded by constructing a nude mouse model of a subcutaneously implanted tumor. miR-195 and miR-497 were expressed to varying degrees in Caco-2, LoVo, and HT-29 cells. Overexpression of miR-195/497 and inhibition of FRA1 decreased HT-29 cell proliferation, inhibited cell invasion and migration, and promoted Epithelial-mesenchymal transition (EMT). In vivo experiments showed that the overexpression of miR-195/497 or inhibition of FRA1 inhibited tumor growth, affected EMT in tumor cells, and inhibited the expression of FRA1. Additionally, the aforementioned conditions had the best effect when used together. The miR-195-497 cluster can regulate the proliferation, EMT, invasion, and migration of colorectal cancer cells by regulating the common target gene FRA1, thereby affecting the development of colorectal cancer.

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References

  1. Dekker, E., Tanis, P. J., Vleugels, J. L. A., Kasi, P. M., & Wallace, M. B. (2019). Colorectal cancer. Lancet, 394(10207), 1467–1480.

    Article  PubMed  Google Scholar 

  2. Carter, J. V., Galbraith, N. J., Yang, D., Burton, J. F., Walker, S. P., & Galandiuk, S. (2017). Blood-based microRNAs as biomarkers for the diagnosis of colorectal cancer: A systematic review and meta-analysis. British Journal of Cancer, 116(6), 762–774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hao, S., Huo, S., Du, Z., Yang, Q., Ren, M., Liu, S., et al. (2019). MicroRNA-related transcription factor regulatory networks in human colorectal cancer. Medicine (Baltimore), 98(15), e15158.

    Article  CAS  PubMed  Google Scholar 

  4. Cojocneanu, R., Braicu, C., Raduly, L., Jurj, A., Zanoaga, O., Magdo, L., et al. (2020). Plasma and tissue specific miRNA expression pattern and functional analysis associated to colorectal cancer patients. Cancers (Basel)., 12(4), 843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Falzone, L., Scola, L., Zanghì, A., Biondi, A., Di Cataldo, A., Libra, M., et al. (2018). Integrated analysis of colorectal cancer microRNA datasets: Identification of microRNAs associated with tumor development. Aging (Albany NY), 10(5), 1000–1014.

    Article  PubMed  Google Scholar 

  6. Lin, X., Wang, S., Sun, M., Zhang, C., Wei, C., Yang, C., et al. (2019). miR-195-5p/NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization. Journal of Hematology & Oncology, 12(1), 20.

    Article  Google Scholar 

  7. Gharib, E., Nasri Nasrabadi, P., & Reza, Z. M. (2020). miR-497-5p mediates starvation-induced death in colon cancer cells by targeting acyl-CoA synthetase-5 and modulation of lipid metabolism. Journal of Cellular Physiology, 235(7–8), 5570–5589.

    Article  CAS  PubMed  Google Scholar 

  8. Jiang, X., **e, H., Dou, Y., Yuan, J., Zeng, D., & **ao, S. (2020). Expression and function of FRA1 protein in tumors. Molecular Biology Reports, 47(1), 737–752.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang, N., Shen, Q., & Zhang, P. (2016). miR-497 suppresses epithelial-mesenchymal transition and metastasis in colorectal cancer cells by targeting fos-related antigen-1. OncoTargets and Therapy, 9, 6597–6604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wu, J., Ji, A., Wang, X., Zhu, Y., Yu, Y., Lin, Y., et al. (2015). MicroRNA-195-5p, a new regulator of Fra-1, suppresses the migration and invasion of prostate cancer cells. Journal of Translational Medicine, 13, 289.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Pidíkova, P., Reis, R., & Herichova, I. (2020). miRNA clusters with down-regulated expression in human colorectal cancer and their regulation. International Journal of Molecular Sciences, 21(13), 4633.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bai, J., Xu, J., Zhao, J., & Zhang, R. (2020). lncRNA SNHG1 cooperated with miR-497/miR-195-5p to modify epithelial-mesenchymal transition underlying colorectal cancer exacerbation. Journal of Cellular Physiology, 235(2), 1453–1468.

    Article  CAS  PubMed  Google Scholar 

  13. Rao, X., Huang, X., Zhou, Z., & Lin, X. (2013). An improvement of the 2ˆ(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. The Biostatistics, Bioinformatics and Biomathematics, 3(3), 71–85.

    PubMed  Google Scholar 

  14. Ladner, C. L., Yang, J., Turner, R. J., & Edwards, R. A. (2004). Visible fluorescent detection of proteins in polyacrylamide gels without staining. Analytical Biochemistry, 326(1), 13–20.

    Article  CAS  PubMed  Google Scholar 

  15. Wang, H. (2020). MicroRNAs and apoptosis in colorectal cancer. International Journal of Molecular Sciences, 21(15), 5353.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Graham, J. S., & Cassidy, J. (2012). Adjuvant therapy in colon cancer. Expert Review of Anticancer Therapy, 12(1), 99–109.

    Article  CAS  PubMed  Google Scholar 

  17. Michael, M. Z., O’Connor, S. M., van Holst Pellekaan, N. G., Young, G. P., & James, R. J. (2003). Reduced accumulation of specific microRNAs in colorectal neoplasia. Molecular Cancer Research, 1(12), 882–891.

    CAS  PubMed  Google Scholar 

  18. To, K. K., Tong, C. W., Wu, M., & Cho, W. C. (2018). MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside. World Journal of Gastroenterology, 24(27), 2949–2973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhang, N., Hu, X., Du, Y., & Du, J. (2021). The role of miRNAs in colorectal cancer progression and chemoradiotherapy. Biomedicine & Pharmacotherapy, 134, 111099.

    Article  CAS  Google Scholar 

  20. Lataniotis, L., Albrecht, A., Kok, F. O., Monfries, C. A. L., Benedetti, L., Lawson, N. D., et al. (2017). CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function. Science and Reports, 7(1), 8585.

    Article  Google Scholar 

  21. Itesako, T., Seki, N., Yoshino, H., Chiyomaru, T., Yamasaki, T., Hidaka, H., et al. (2014). The microRNA expression signature of bladder cancer by deep sequencing: The functional significance of the miR-195/497 cluster. PLoS ONE, 9(2), e84311.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Flavin, R. J., Smyth, P. C., Laios, A., O’Toole, S. A., Barrett, C., Finn, S. P., et al. (2009). Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma. Modern Pathology, 22(2), 197–205.

    Article  CAS  PubMed  Google Scholar 

  23. Hong, S., Yan, Z., Wang, H., Ding, L., & Bi, M. (2019). Up-regulation of microRNA-497-5p inhibits colorectal cancer cell proliferation and invasion via targeting PTPN3. Bioscience Reports. https://doi.org/10.1042/BSR20191123

  24. Bayat, A., Raad, M., Sharafshah, A., Ahmadvand, M., & Aminian, H. (2022). Identification of miR-195-5p as a novel prognostic biomarker for colorectal cancer. Molecular Biology Reports, 49(7), 6453–6457.

    Article  CAS  PubMed  Google Scholar 

  25. Singh, A., & Settleman, J. (2010). EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene, 29(34), 4741–4751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Carstens, J. L., Lovisa, S., & Kalluri, R. (2014). Microenvironment-dependent cues trigger miRNA-regulated feedback loop to facilitate the EMT/MET switch. The Journal of Clinical Investigation, 124(4), 1458–1460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ning, X., Wang, C., Zhang, M., & Wang, K. (2019). Ectopic expression of miR-147 Inhibits stem cell marker and epithelial-mesenchymal transition (EMT)-related protein expression in colon cancer cells. Oncology Research, 27(4), 399–406.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Vu, T., & Datta, P. K. (2017). Regulation of EMT in colorectal cancer: A culprit in metastasis. Cancers (Basel), 9(12), 171.

    Article  PubMed  Google Scholar 

  29. **ng, Y., **g, H., Zhang, Y., Suo, J., & Qian, M. (2020). MicroRNA-141-3p affected proliferation, chemosensitivity, migration and invasion of colorectal cancer cells by targeting EGFR. International Journal of Biochemistry & Cell Biology, 118, 105643.

    Article  CAS  Google Scholar 

  30. Liu, Z., Liu, X., Li, Y., Ren, P., Zhang, C., Wang, L., et al. (2019). miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression. Cancer Management Research, 11, 5317–5332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Shuai, F., Wang, B., & Dong, S. (2018). MicroRNA-204 inhibits the growth and motility of colorectal cancer cells by downregulation of CXCL8. Oncology Research, 26(8), 1295–1305.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wang, L., Guo, J., Zhou, J., Wang, D., Kang, X., & Zhou, L. (2020). NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2. Journal of Experimental & Clinical Cancer Research, 39(1), 225.

    Article  CAS  Google Scholar 

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Authors

Contributions

LH and WD conceptualized, designed the study and write manuscript. HW responsible for data collection and analysis. JZ responsible for article checking literature search.

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Correspondence to Jia Zheng.

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All authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the ethics committee of Wuhan Myhalic Biotechnology Co., Ltd (HLK-20220520-005). All animal experiments are in compliance with the relevant regulations of the Hubei Provincial Animal Management Committee “Experimental Animal Ethics Certificate”. This article does not contain any studies with human participants performed by any of the authors.

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Huang, L., Ding, W., Wu, H. et al. miR-497/195 Cluster Affects the Development of Colorectal Cancer by Targeting FRA1. Mol Biotechnol 66, 1019–1030 (2024). https://doi.org/10.1007/s12033-023-01000-w

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