Metastasis inhibition by BRMS1 and miR-31 replacement therapy in claudin-low cell lines

Document Type : Original Article

Authors

1 Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Biotechnology, Science and Research Branch, Islamic Azad Unversity, Tehran, Iran

3 Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for StemCell Biology and Technology, ACECR, Tehran, Iran

Abstract

Objective(s): The growing trend of research demonstrates that dynamic expression of two metastasis repressor classes (metastasis suppressor genes and anti-metastatic miRNA) has a close relationship with tumor invasion and metastasis. Using different strategies, it was revealed that cellular levels of miR-31 and Breast cancer Metastasis Suppressor1 (BRMS1) protein, which are among the most significant modulators of metastasis, have a correlation with the cell’s capability for invading and metastasizing; cells containing higher levels of miR-31 or BRMS1 were less metastatic. This project was carried out to determine whether the combinations of miR-31 and BRMS1 genes are able to enhance the capability of repressing the claudin-low breast cancer cell (MDA-MB-231) invasion. Materials and Methods: This study used a restoration-based approach by miR-31 mimic and optimized BRMS1 gene sequences, which were cloned into a chimeric construct and transfected to the MDA-M231cells.
Results: Our data revealed that the simultaneous expression of anti-metastasis miR and metastasis suppressor might inhibit migration and invasion in MDA-MB-231 cells efficiently.
Conclusion: This combinatorial use of anti-metastatic miR and gene suggests a new therapeutic intervention for metastasis inhibition in MDA-MB-231.

Keywords


1. Kodura MA, Souchelnytskyi S. Breast carcinoma metastasis suppressor gene 1 (BRMS1): update on its role as the suppressor of cancer metastases. Cancer Metastasis Rev 2015; 34:611-618.
2. Welch D, Manton C, Hurst D. Breast Cancer Metastasis Suppressor 1 (BRMS1): Robust biological and pathological data, but still enigmatic mechanism of action. Adv Cancer Res 2016; 132:111-137.
3. Hashemi ZS, Moghadam MF, Khalili S, Ghavami M, Salimi F, Sadroddiny E. Additive effect of metastamiR-193b and breast cancer metastasis suppressor 1 as an anti-metastatic strategy. Breast Cancer 2019; 26:215-228.
4. Edmonds MD, Hurst DR, Vaidya KS, Stafford LJ, Chen D, Welch DR. Breast cancer metastasis suppressor 1 coordinately regulates metastasis‐associated microRNA expression. Int J Cancer 2009; 125:1778-1785.
5. Edmonds MD, Hurst DR, Welch DR. Linking metastasis suppression with metastamiR regulation. Cell cycle 2009; 8:2673-2675.
6. Hashemi ZS, Khalili S, Forouzandeh Moghadam M, Sadroddiny E. Lung cancer and miRNAs: a possible remedy for anti-metastatic, therapeutic and diagnostic applications. Expert Rev Respir Med 2017; 11:147-157.
7. Schmittgen TD. miR-31: a master regulator of metastasis? Future Oncol 2010; 6:17-20.
8. Körner C, Keklikoglou I, Bender C, Wörner A, Münstermann E, Wiemann S. MicroRNA-31 sensitizes human breast cells to apoptosis by direct targeting of protein kinase C ϵ (PKCϵ). J Biol Chem 2013; 288:8750-8761.
9. Farokhimanesh S, Forouzandeh Moghadam M, Ebrahimi M. Inhibition of breast cancer metastasis by using miR-31-mimic in cancer stem cell rich MDA-MB231 cell line.Tehran Univ Med J 2015; 73:1-10.
10. Sossey‐Alaoui K, Downs‐Kelly E, Das M, Izem L, Tubbs R, Plow EF. WAVE3, an actin remodeling protein, is regulated by the metastasis suppressor microRNA, miR‐31, during the invasion‐metastasis cascade. Int J Cancer 2011; 129:1331-1343.
11. Augoff K, Das M, Bialkowska K, McCue B, Plow EF, Sossey-Alaoui K. MiR-31 is a broad regulator of β1-integrin expression and function in cancer cells. Mol Cancer Res 2011; 9:1500-1508.
12. Luo LJ, Yang F, Ding JJ, Yan DL, Wang DD, Yang SJ, et al. MiR-31 inhibits migration and invasion by targeting SATB2 in triple negative breast cancer. Gene 2016; 594:47-58.
13. Hashemi ZS, Moghadam MF, Farokhimanesh S, Rajabibazl M, Sadroddiny E. Inhibition of breast cancer metastasis by co-transfection of miR-31/193b-mimics. Iran J Basic Med Sci 2018; 21:427-433.
14. Hashemi ZS, Moghadam MF, Sadroddiny E. Varying miR-193b-3p expression patterns in breast cancer cell Lines indicates its potential for cancer management strategies. Int J Cancer Manag 2018; 11:1-9.
15. Henry JC, Azevedo-Pouly ACP, Schmittgen TD. MicroRNA replacement therapy for cancer. Pharm Res 2011; 28:3030-3042.
16. Kasinski AL, Slack FJ. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer 2011; 11:849-864.
17. Kay MA. State-of-the-art gene-based therapies: the road ahead. Nat Rev Genet 2011; 12:316-328.
18. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 2007; 39:673-677.
19. van Rooij E, Purcell AL, Levin AA. Developing microRNA therapeutics. Circ Res 2012; 110:496-507.
20. Dittmer J. Mechanisms governing metastatic dormancy in breast cancer. Semin Cancer Biol 2017; 44:72-82.
21. Idowu MO, Kmieciak M, Dumur C, Burton RS, Grimes MM, Powers CN, et al. CD44+/CD24−/low cancer stem/progenitor cells are more abundant in triple-negative invasive breast carcinoma phenotype and are associated with poor outcome. Hum Pathol 2012; 43:364-373.
22. Mylona E, Giannopoulou I, Fasomytakis E, Nomikos A, Magkou C, Bakarakos P, et al. The clinicopathologic and prognostic significance of CD44+/CD24−/low and CD44−/CD24+ tumor cells in invasive breast carcinomas. Hum Pathol 2008; 39:1096-1102.
23. Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, et al. CD44+/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 2006; 8: R59.
24. Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005; 65:5506-5511.
25. Raza U, Zhang JD, Şahin Ö. MicroRNAs: master regulators of drug resistance, stemness, and metastasis. J Mol Med 2014; 92:321-336.
26. Valastyan S, Weinberg RA. MiR-31: a crucial overseer of tumor metastasis and other emerging roles. Cell Cycle 2010; 9:2124-2129.
27. Zhang Y, Ye L, Tan Y, Sun P, Ji K, Jiang WG. Expression of breast cancer metastasis suppressor-1, BRMS-1, in human breast cancer and the biological impact of BRMS-1 on the migration of breast cancer cells. Anticancer Res 2014; 34:1417-1426.