MiR-21 and mRNA PTEN Expression Levels and Biomarker Potential in Breast Cancer
DOI:
https://doi.org/10.31964/mltj.v7i1.364Keywords:
MiR-21, mRNA PTEN, Real-Time qPCRAbstract
MiR-21 has been linked to tumorigenesis, development, and metastasis in tumor pathogenesis. All human cancers, including breast cancer, have increased expression of MiR-21, which is the only miRNA that has increased expression. PTEN expression was found to be reduced in the majority of solid tumors, including breast cancer. Since lymph node metastatic factors, estrogen receptor status, tumor grade, and tumor node metastasis (TNM) all decreased PTEN expression, the PTEN expression profile may be a very useful prognostic marker in breast cancer. PTEN inhibits PIP3 (phosphatidylinositol 3,4,5-triphosphate) activity by having protein phosphatase and lipid phosphatase activity that is the polar opposite of PI3K (Phosphatidyl Inositol 3-Kinase). The aim of this research was to see how often miR-21 and mRNA PTEN were expressed at different stages of breast cancer and whether they could be used as prognostic markers. This type of research is an observational study with a cross-sectional design. The sample size of 43 people came from breast cancer patients. Analysis of miR-21 expression and mRNA PTEN using Real-Time qPCR. The results showed that miR-21 expression increased 1.32 times at an advanced stage compared to an early stage, while mRNA PTEN expression decreased 1.33 fold at an advanced stage compared to an early stage. According to the findings, miR-21 expression in the blood plasma of breast cancer patients was upregulated at an advanced stage compared to an early stage and downregulated mRNA PTEN expression. MiR-21 which is increased at an advanced stage has the potential to be a poor prognostic marker at the stage of breast cancer. The change in miR-21 expression can be a good candidate as a molecular prognostic marker and for future research the role of miR-21 in breast cancer progression will further enrich the scientific repertoire, especially in the health and clinical fields.References
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Anwar, S. L., Tanjung, D. S., Fitria, M. S., Kartika, A. I., Sari, D. N. I., Rakhmina, D., Wardana, T., Astuti, I., Haryana, S. M., & Aryandono, T. (2020). Dynamic Changes of Circulating Mir-155 Expression and the Potential Application as a Non-Invasive Biomarker in Breast Cancer. Asian Pacific Journal of Cancer Prevention : APJCP, 21(2), 491–497. https://doi.org/10.31557/APJCP.2020.21.2.491
Arroyo, J. D., Chevillet, J. R., Kroh, E. M., Ruf, I. K., Pritchard, C. C., Gibson, D. F., Mitchell, P. S., Bennett, C. F., Pogosova-Agadjanyan, E. L., Stirewalt, D. L., Tait, J. F., & Tewari, M. (2011). Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proceedings of the National Academy of Sciences of the United States of America, 108(12), 5003–5008. https://doi.org/10.1073/pnas.1019055108
Chan, J. A., Krichevsky, A. M., & Kosik, K. S. (2005). MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Research, 65(14), 6029–6033. https://doi.org/10.1158/0008-5472.CAN-05-0137
Cheang, M. C. U., Chia, S. K., Voduc, D., Gao, D., Leung, S., Snider, J., Watson, M., Davies, S., Bernard, P. S., Parker, J. S., Perou, C. M., Ellis, M. J., & Nielsen, T. O. (2009). Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. Journal of the National Cancer Institute, 101(10), 736–750. https://doi.org/10.1093/jnci/djp082
Heneghan, H. M., Miller, N., & Kerin, M. J. (2010). MiRNAs as biomarkers and therapeutic targets in cancer. Current Opinion in Pharmacology, 10(5), 543–550. https://doi.org/10.1016/j.coph.2010.05.010
Huang, G., Zhang, X., Guo, G., & Huang, K. (2009). Clinical significance of miR-21 expression in breast cancer : of invasive ductal carcinoma. Oncology Reports, 21(2), 673–679. https://doi.org/10.3892/or
Li, L. Q., Li, X. L., Wang, L., Du, W. J., Guo, R., Liang, H. H., Liu, X., Liang, D. Sen, Lu, Y. J., Shan, H. L., & Jiang, H. C. (2012). Matrine inhibits breast cancer growth via miR-21/PTEN/Akt pathway in MCF-7 cells. Cellular Physiology and Biochemistry, 30(3), 631–641. https://doi.org/10.1159/000341444
Li, M., Li, J., Ding, X., He, M., & Cheng, S.-Y. (2010). microRNA and cancer. The AAPS Journal, 12(3), 309–317. https://doi.org/10.1208/s12248-010-9194-0
Lowery, A. J., Miller, N., Devaney, A., McNeill, R. E., Davoren, P. A., Lemetre, C., Benes, V., Schmidt, S., Blake, J., Ball, G., & Kerin, M. J. (2009). MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Research, 11(3), 1–18. https://doi.org/10.1186/bcr2257
Meng, F., Henson, R., Wehbe-Janek, H., Ghoshal, K., Jacob, S. T., & Patel, T. (2007). MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology, 133(2), 647–658. https://doi.org/10.1053/j.gastro.2007.05.022
Mitchell, P. S., Parkin, R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan, E. L., Peterson, A., Noteboom, J., O’Briant, K. C., Allen, A., Lin, D. W., Urban, N., Drescher, C. W., Knudsen, B. S., Stirewalt, D. L., Gentleman, R., Vessella, R. L., Nelson, P. S., Martin, D. B., & Tewari, M. (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences of the United States of America, 105(30), 10513–10518. https://doi.org/10.1073/pnas.0804549105
Mo, M.-H., Chen, L., Fu, Y., Wang, W., & Fu, S. W. (2012). Cell-free Circulating miRNA Biomarkers in Cancer. Journal of Cancer, 3, 432–448. https://doi.org/10.7150/jca.4919
Negrini, M., & Calin, G. A. (2008). Breast cancer metastasis: A microRNA story. Breast Cancer Research, 10(2), 2–5. https://doi.org/10.1186/bcr1867
Pan, X., Wang, Z. X., & Wang, R. (2010). MicroRNA-21: A novel therapeutic target in human cancer. Cancer Biology and Therapy, 10(12), 1224–1232. https://doi.org/10.4161/cbt.10.12.14252
Radojicic, J., Zaravinos, A., Vrekoussis, T., Kafousi, M., Spandidos, D. A., & Stathopoulos, E. N. (2011). MicroRNA expression analysis in triple-negative (ER, PR and Her2/neu) breast cancer. Cell Cycle, 10(3), 507–517. https://doi.org/10.4161/cc.10.3.14754
Schwarzenbach, H., Milde-Langosch, K., Steinbach, B., Müller, V., & Pantel, K. (2012). Diagnostic potential of PTEN-targeting miR-214 in the blood of breast cancer patients. Breast Cancer Research and Treatment, 134(3), 933–941. https://doi.org/10.1007/s10549-012-1988-6
Song, M. S., Salmena, L., & Pandolfi, P. P. (2012). The functions and regulation of the PTEN tumour suppressor. Nature Reviews. Molecular Cell Biology, 13(5), 283–296. https://doi.org/10.1038/nrm3330
Tran, B., & Bedard, P. L. (2011). Luminal-B breast cancer and novel therapeutic targets. Breast Cancer Research, 13(6). https://doi.org/10.1186/bcr2904
Turchinovich, A., Weiz, L., Langheinz, A., & Burwinkel, B. (2011). Characterization of extracellular circulating microRNA. Nucleic Acids Research, 39(16), 7223–7233. https://doi.org/10.1093/nar/gkr254
Wickramasinghe, N. S., Manavalan, T. T., Dougherty, S. M., Riggs, K. a., Li, Y., & Klinge, C. M. (2009). Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. Nucleic Acids Research, 37(8), 2584–2595. https://doi.org/10.1093/nar/gkp117
Yan, L.-X., Huang, X.-F., Shao, Q., Huang, M.-Y., Deng, L., Wu, Q.-L., Zeng, Y.-X., & Shao, J.-Y. (2008). MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA (New York, N.Y.), 14(11), 2348–2360. https://doi.org/10.1261/rna.1034808
Zhang, J., Wang, J., Zhao, F., Liu, Q., Jiang, K., & Yang, G. (2010). MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clinica Chimica Acta; International Journal of Clinical Chemistry, 411(11–12), 846–852. https://doi.org/10.1016/j.cca.2010.02.074
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2021-06-18
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Rakhmina, D., Haryana, S. M., & Aryandono, T. (2021). MiR-21 and mRNA PTEN Expression Levels and Biomarker Potential in Breast Cancer. Medical Laboratory Technology Journal, 7(1), 46–58. https://doi.org/10.31964/mltj.v7i1.364
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