MiR-21 and mRNA PTEN Expression Levels and Biomarker Potential in Breast Cancer

Dinna Rakhmina, Sofia Mubarika Haryana, Teguh Aryandono


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.


MiR-21; mRNA PTEN; Real-Time qPCR

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Andorfer, C. a., Necela, B. M., Thompson, E. A., & Perez, E. a. (2011). MicroRNA signatures: Clinical biomarkers for the diagnosis and treatment of breast cancer. Trends in Molecular Medicine, 17(6), 313–319. https://doi.org/10.1016/j.molmed.2011.01.006

Anwar, S. L., Sari, D. N. I., Kartika, A. I., Fitria, M. S., Tanjung, D. S., Rakhmina, D., Wardana, T., Astuti, I., Haryana, S. M., & Aryandono, T. (2019). Upregulation of circulating MiR-21 expression as a potential biomarker for therapeutic monitoring and clinical outcome in breast cancer. Asian Pacific Journal of Cancer Prevention, 20(4), 1223–1228. https://doi.org/10.31557/APJCP.2019.20.4.1223

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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