Investigating the Relation between miR-31 and RhoA Expressions in Breast Cancer Clinical Samples and Cell Lines: A Controversial Matter
Trends in Peptide and Protein Sciences,
Vol. 1 No. 3 (2017),
8 May 2017
,
Page 123-129
https://doi.org/10.22037/tpps.v1i3.16835
Abstract
Breast cancer is the most prevalent diagnosed cancer and the second cause of cancer death among women worldwide. There are different mechanisms that play crucial roles in the onset and progression of breast cancer including microRNAs. microRNAs are small noncoding RNAs that regulate gene expression by repressing translation post-transcriptionally. miR-31 is an integrin modulator implicated in different cellular processes such as apoptosis, cell cycle control, and DNA repair. According to the literature, RhoA is one of the genes regulated by miR-31. It has an important role in actin-myosin contraction and subsequently in cell motility and migration in metastasis cascade. Breast cancer cell lines, MCF-7 and MDA-MB-231, as well as normal breast cells, MCF-10A, were cultured. RNA extraction, cDNA synthesis, and SYBR Green I quantitative real-time PCR were used to investigate the expression of miR-31 and RhoA. In addition, 10 metastatic breast cancer clinical samples were analyzed to assess miR-31 and RhoA expression, and normal cells from the same patients were used as controls. Pearson’s correlation co-efficient was applied to find out any probable relation between miR-31 and RhoA expression. Gene expression analyses in MCF-7 cell line showed downregulation of miR-31 while RhoA was upregulated in the cell line (inverse correlation). miR-31 and RhoA were both upregulated in metastatic MDA-MB-231 cell line and downregulated in 90% of clinical samples. Pearson’s correlation co-efficient showed complete positive correlation between miR-31 and RhoA expression. The expression of miR-31 and RhoA is positively correlated, and it is declined in metastatic breast that cancer clinical samples save MDA-MB-231 cells. Unlike previous reports, we found that miR-31 is not the main silencer of RhoA expression. Therefore, more investigation on genes and miRNAs affecting metastasis process can elucidate new biomarkers and therapeutic targets for metastatic breast cancer.
Highlights
- miR-31 is an important miRNA implicated in different cellular processes as well as cancer.
- The protein product of RhoA gene plays a role in actin-myosin contraction and cell motility in cancer metastasis.
- We approved bioinformatically and experimentally that RhoA is one of the genes regulated by miR-31
- miR-31
- RhoA
- Breast cancer
- Metastasis
How to Cite
References
Augoff, K., Das, M., Bialkowska, K., McCue, B., Plow, E.F. and K. Sossey-Alaoui, (2011). "miR-31 is a broad regulator of beta1-integrin expression and function in cancer cells." Molecular Cancer Research, 9 (11): 1500-1508.
Chen, M., Bresnick, A.R. and K. L. O'Connor, (2013) "Coupling S100A4 to Rhotekin alters Rho signaling output in breast cancer cells." Oncogene, 32 (32): 3754-3764.
Howe, L. R. and A. M. Brown, (2004). "Wnt signaling and breast cancer." Cancer Biology & Therapy, 3 (1): 36-41.
Laurila, E. M. and A. Kallioniemi, (2013) "The diverse role of miR-31 in regulating cancer associated phenotypes." Genes Chromosomes Cancer, 52 (12): 1103-1113.
Lu, Z., Ye, Y., Jiao, D., Qiao, J., Cui, S. and Z. Liu, (2012). "miR-155 and miR-31 are differentially expressed in breast cancer patients and are correlated with the estrogen receptor and progesterone receptor status." Oncology Letters, 4 (5): 1027-1032.
Marino, N., Woditschka, S., Reed,L.T., Nakayama, J., Mayer, M., Wetzel, M. and P. S. Steeg, (2013). "Breast cancer metastasis: issues for the personalization of its prevention and treatment." The American Journal of Pathology, 183 (4): 1084-1095.
Mohammadi-Yeganeh, S., Mansouri, A. and M. Paryan, (2015). "Targeting of miR9/NOTCH1 interaction reduces metastatic behavior in triple-negative breast cancer." Chemical Biology & Drug Design, 86 (5): 1185-1191.
Mohammadi-Yeganeh, S., Paryan, M., Arefian, E., Vasei, M., Ghanbarian, H., Mahdian, R., Karimipoor, M. and M. Soleimani, (2016). "MicroRNA-340 inhibits the migration, invasion, and metastasis of breast cancer cells by targeting Wnt pathway." Tumor Biology, 37 (7): 8993-9000.
Mohammadi-Yeganeh, S., Paryan, M., Mirab Samiee, S., Soleimani, M., Arefian, E., Azadmanesh, K., Mostafavi, E., Mahdian, R. and M. Karimipoor, (2013). "Development of a robust, low cost stem-loop real-time quantification PCR technique for miRNA expression analysis." Molecular Biology Reports, 40 (5): 3665-3674.
Mulrane, L., Gallagher, W.M. and D. P. O'Connor, (2014). "A novel mechanism of regulation of the anti-metastatic miR-31 by EMSY in breast cancer." Breast Cancer Research, 16 (6): 467.
Nwabo Kamdje, A.H., Seke Etet, P.F., Vecchio, L., Tagne, R.S., Amvene, J.M., Muller, J.M., Krampera, M. and K. E. Lukong, (2014). "New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers." World Journal of Clinical Cases, 2 (2): 769-786.
O'Connor, K. and M. Chen, (2013). "Dynamic functions of RhoA in tumor cell migration and invasion." Small GTPases, 4 (3): 141-147.
Pfaffl, M. W., Horgan, G.W. and L. Dempfle, (2002). "Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR." Nucleic Acids Research, 30 (9): e36.
Pourteimoor, V., Mohammadi-Yeganeh, S. and M. Paryan, (2016). "Breast cancer classification and prognostication through diverse systems along with recent emerging findings in this respect; the dawn of new perspectives in the clinical applications." Tumor Biology, 37 (11): 14479-14499.
Rasheed, S. A., Teo, C.R., Beillard, E.J., Voorhoeve, P.M., Zhou, W., Ghosh, S. and P. J. Casey, (2015). "MicroRNA-31 controls G protein alpha-13 (GNA13) expression and cell invasion in breast cancer cells." Molecular Cancer, 14: 67.
Reddy, K. B. (2015). "MicroRNA (miRNA) in cancer." Cancer Cell International, 15: 38.
Roartsy, K. and J. M. Rosen, (2010). "Wnt and mammary stem cells: hormones cannot fly wingless". Current Opinion Pharmacology, 10 (6): 643-649.
Schmittgen, T. D. (2010). "miR-31: a master regulator of metastasis?" Future Oncology, 6(1): 17-20.
Takahashi, R. U., Miyazaki, H. and T. Ochiya, (2015). "The Roles of MicroRNAs in Breast Cancer." Cancers (Basel) 7 (2): 598-616.
Takebe, N., Warren, R.Q. and S. P. Ivy, (2011). "Breast cancer growth and metastasis: interplay between cancer stem cells, embryonic signaling pathways and epithelial-to-mesenchymal transition." Breast Cancer Research, 13 (3): 211.
Valastyan, S., Benaich, N., Chang, A., Reinhardt, F. and R. A. Weinberg, (2009). "Concomitant suppression of three target genes can explain the impact of a microRNA on metastasis." Genes & Development, 23 (22): 2592-2597.
Valastyan, S., Reinhardt, F., Benaich, N., Calogrias, D., Szasz, A.M., Wang, Z.C., Brock, J.E., Richardson, A.L., and R. A. Weinberg, (2009). "A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis." Cell, 137 (6): 1032-1046.
Valastyan, S. and R. A. Weinberg, (2010). "miR-31: a crucial overseer of tumor metastasis and other emerging roles." Cell Cycle, 9 (11): 2124-2129.
Yi, T., Zhai, B., Yu, Y., Kiyotsugu, Y., Raschle, T., Etzkorn, M., Seo, H.C., Nagiec, M., Luna, R.E., Reinherz, E.L., Blenis, J., Gygi, S.P. and G. Wagner, (2014). "Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells." Proceedings of the National Academy of Sciences of the United States of America, 111 (21): E2182-2190.
- Abstract Viewed: 633 times
- PDF Downloaded: 303 times