Cancer Prognosis and miRNA
Year 2025,
Volume: 6 Issue: 3, 1 - 14, 01.08.2025
Faten Alnoaimi
,
Mehmet Özaslan
Abstract
The micro ribonucleic acids are commonly referred to as MicroRNAs, miRNAs or μRNA. These micro-nucleic acids are very short and single-stranded RNA molecules composed by 19 to 25 nucleotides. miRNAs play an important regulatory role in the cells of many organisms including humans, animals, and plants. miRNAs were discovered in 1993 and the role and mechanism of action of these molecules is still under investigation. Recently, it has been confirmed that the non-coding miRNAs play an essential role in gene regulation. Considering the role of miRNAs in many biological and pathological reactions and mechanisms, especially cancer, scientific interest in these molecules is increasing as these molecules are believed to hold great promise as a therapeutic approach. The discovery of miRNAs is considered as the beginning of a new age in molecular biology. This article will provide an outlook on miRNAs, the stages of their biogenesis, types of miRNAs and their role in cancer initiation and progression. Therefore, the aim of this research is to identify the biological mechanisms by which miRNAs can influence cellular functions that are disrupted in the initiation and progression of cancer. In addition, this research also aims to demonstrate the potential of utilizing miRNAs in the diagnosis and therapy of different types of cancer.
Ethical Statement
This paper does not require ethics committee approval
Supporting Institution
No support was received for this study
References
-
Ali Syeda, Z., Langden, S. S. S., Munkhzul, C., Lee, M., and Song, S. J. (2020). Regulatory mechanism of MicroRNA expression in cancer. International journal of molecular sciences, 21(5), 1723. doi: 10.3390/ijms21051723
-
Amaral, F. C., Torres, N., Saggioro, F., Neder, L., Machado, H. R., Silva Jr, W. A. and Castro, M. (2009). MicroRNAs differentially expressed in ACTH-secreting pituitary tumors. The Journal of Clinical Endocrinology & Metabolism, 94(1), 320-323. 10.1210/jc.2008-1451
-
Bao, C., Chen, J., Chen, D., Lu, Y., Lou, W., Ding, B., Xu, L., and Fan, W. (2020). MiR-93 suppresses tumorigenesis and enhances chemosensitivity of breast cancer via dual targeting E2F1 and CCND1. Cell Death & Disease, 11(8), 3166–3177. 10.1111/jcmm.14171
-
Bašová, P., Pešta, M., Sochor, M., and Stopka, T. (2017). Prediction potential of serum mir-155 and mir-24 for relapsing early breast cancer. Int. J. Mol. Sci., 18, 1–10. 10.3390/ijms18102116
-
Breunig, C., Pahl, J., Küblbeck, M., Miller, M., Antonelli, D., Erdem, N., and Wiemann, S. (2017). MicroRNA-519a-3p mediates apoptosis resistance in breast cancer cells and their escape from recognition by natural killer cells. Cell death & disease, 8(8), e2973-e2973. 10.1038/cddis.2017.364
-
Calin, G. A., Cimmino, A., Fabbri, M., Ferracin, M., Wojcik, S. E., Shimizu, M. and Alder, H. (2008). MiR-15a and miR-16-1 cluster functions in human leukemia. Proceedings of the National Academy of Sciences, 105(13), 5166-5171. https://doi.org/10.1073/pnas.080012110
-
Calin, G. A., Dumitru, C. D., Shimizu, M., Bichi, R., Zupo, S., Noch, E. and Rassenti, L. (2002). Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the national academy of sciences, 99(24), 15524-15529. 10.1073/pnas.242606799
-
Calin, G. A., Ferracin, M., Cimmino, A., Di Leva, G., Shimizu, M., Wojcik, S. E. and Iuliano, R. (2005). A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. New England Journal of Medicine, 353(17), 1793-1801. 10.1056/NEJMoa050995
-
Cameron, J. E., Yin, Q., Fewell, C., Lacey, M., McBride, J., Wang, X. and Flemington, E. K. (2008). Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. Journal of virology, 82(4), 1946-1958. 10.1128/JVI.02136-07
-
Catalanotto, C., Cogoni, C., and Zardo, G. (2016). MicroRNA in control of gene expression: an overview of nuclear functions. International journal of molecular sciences, 17(10), 1-17. 10.3390/ijms17101712
-
Chen, J., Wang, B. C., and Tang, J. H. (2012). Clinical significance of micoRNA-155 expression in human breast cancer. Journal of surgical oncology, 106(3), 260-266.
-
Chen, P., Xu, W., Luo, Y., Zhang, Y., He, Y., Yang, S., and Yuan, Z. (2017). MicroRNA 543 suppresses breast cancer cell proliferation, blocks cell cycle and induces cell apoptosis via direct targeting of ERK/MAPK. OncoTargets and therapy, 6(10), 1423-1431. 10.2147/OTT.S118366
-
Corcoran, C., Rani, S., Breslin, S., Gogarty, M., Ghobrial, I. M., Crown, J., O'Driscoll, L. (2014). miR-630 targets IGF1R to regulate response to HER-targeting drugs and overall cancer cell progression in HER2 over-expressing breast cancer. Molecular Cancer, 234(3), 2880–2894. 10.1186/1476-4598-13-71
-
Dharanija, M., Katarina, C., Burwinkel, B., and Rongxi, Y. (2013). Cancer diagnosis andprognosis decoded by blood-based circulating microRNA signatures. Front.Genet, 4, 116–127. 10.3389/fgene.2013.00116
-
Dinçer, B. C. (2023). Investigation of miRNA molecules as biomarkers in the diagnosis of breast cancer. (Master's Thesis) İstanbul University the Institute of Health Sciences, İstanbul, Türkiye.
-
Elnaggar, G. N., El-Hifnawi, N. M., Ismail, A., Yahia, M., Elshimy, R. A. A. (2021). Micro RNA-148a targets Bcl-2 in patients with non-small cell lung cancer. Asian Pacific J Cancer Prev, 22(6), 1949–1955. 10.31557/ APJCP.2021.22.6.1949
Elton, T. S., Selemon, H., Elton, S. M., and Parinandi, N. L. (2012). Regulation of the MIR155 host gene in physiological and pathological processes. Gene., 18, 1–63. 10.1016/j.gene.2012.12.009
-
Feng, H., Ge, F., Du, L., Zhang, Z., and Liu, D. (2019). MiR - 34b - 3p Represses Cell Proliferation, Cell Cycle Progression and Cell Apoptosis in Non - Small -Cell Lung Cancer (NSCLC) by Targeting CDK4. J Cell Mol Med, 23(8), 5282–5291. 10.1111/jcmm.14404
-
Friedländer, M. R., Lizano, E., J S Houben, A. J. S., Bezdan, D., Báñez-Coronel, M., Kudla, G., Mateu-Huertas, E., Kagerbauer, B., González, J., Chen, K. C., LeProust, E. M., Martí, E., and Estivill, X. (2014). Evidence for the biogenesis of more than 1,000 novel human microRNAs. Genome biology, 15, 1-17. 10.1186/gb-2014-15-4-r57
-
Fu, X., Yin, Y., Zhang, M., Peng, F., Shi, Y., Liu, Y., Tan, Y., Zhao, Z., Yin, X., Song, J., Ke, G., and Zhang, X. (2021). Size-selective DNA nanocage-based activatable CRISPR-Cas12a for sensitive and accurate detection of mature microRNA. Chemical Communications, 57(26), 3291–3294. 10.1039/d1cc00178g
-
Garrido-Cano, I., Pattanayak, B., Adam-Artigues, A., Lameirinhas, A., Torres-Ruiz, S., Tormo, E., Cervera, R., and Eroles, P. (2022). MicroRNAs as a clue to overcome breast cancer treatment resistance. Cancer and Metastasis Reviews, 41, 77-105. https://doi.org/10.1007/s10555-021-09992-0
-
Gomez, G. G., Wykosky, J., Zanca, C., Furnari, F. B., and Cavenee, W. K. (2013). Therapeutic resistance in cancer: MicroRNA regulation of EGFR signaling networks. Cancer Biology & Medicine, 10(4), 192–205. 10.7497/j.issn.2095-3941.2013.04.003
-
Gonzalez-Alegre, P. (2007). Therapeutic RNA interference for neurodegenerative diseases: From promise to progress. Pharmacology & therapeutics, 114(1), 34-55. 10.1016/j.pharmthera.2007.01.003
-
Grace, L., Phoebe, M., and Jemmy Christy, H. (2024). Utilizing oncomir and tsmir as biomarkers for screening breast cancer. Current Trends in Biotechnology and Pharmacy, 18(Supplementry Issue 4A), 18–30. 10.5530/ctbp.2024.4s.2
-
Hammond, S. M. (2015). An overview of microRNAs. Adv Drug Deliv Rev, 87, 3–14. 10.1016/j.addr.2015.05.001
-
Hartmann, P., and Tacke, F. (2016). Tiny RNA with great effects: miR-155 in alcoholic liver disease. Journal of Hepatology, 64, 1214–1216. http://dx.doi.org/10.1016/j.jhep.2016.01.035
-
Hayes, J., Peruzzi, P. P. and Lawler, S. (2014). MicroRNAs in cancer: biomarkers, functions and therapy. Trends in molecular medicine, 20(8), 460-469. 10.1016/j.molmed.2014.06.005
-
He, b., Zhao, Z., Cai, Q., Zhang, Y., Zhang, P., Shi, S., Xie, H., Peng, X., Yin, W., Tao, Y., and Wang, X. (2020). miRNA-based biomarkers, therapies, and resistance in cancer. International Journal of Biological Sciences, 16(14), 2628− 2647. 10.7150/ijbs.47203
-
Hussen, B. M., Hidayat, H. J., Salihi, A., Sabir, D. K., Mohammad Taheri, M., and Ghafouri-Fard, S. (2021). MicroRNA: A signature for cancer progression. Biomedicine & Pharmacotherapy, 138, 1−11. https://doi.org/10.1016/j.biopha.2021.111528
-
Iorio, M. V., Ferracin, M., Liu, C. G., Veronese, A., Spizzo, R., Sabbioni, S. and Ménard, S. (2005). MicroRNA gene expression deregulation in human breast cancer. Cancer research, 65(16), 7065-7070. 10.1158/0008-5472.CAN-05-1783
-
Jia, C. Y., Li, H. H., Zhu, X. C., Dong, Y. W., Fu, D., Zhao, Q. L., Wu, W., Wu, X. Z. (2011). MiR-223 Suppresses Cell Proliferation by Targeting IGF-1R. PloS one, 6(11), 1-13. 10.1371/journal.pone.0027008
-
Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A. and Slack, F. J. (2005). RAS is regulated by the let-7 microRNA family. Cell, 120(5), 635-647. 10.1016/j.cell.2005.01.014
-
Karagün, B. Ş., Antmen, B., Şaşmaz, İ. and Kılınç, Y. (2014). Mikro RNA and Cancer. Türk Klinik Biyokimya, 12(1), 45-56.
Kim, K., Chadalapaka, G., Lee, S. O., Yamada, D., Sastre-Garau, X., Defossez, P. A., Park, Y. Y., Lee, J. S., and Safe, S. (2012). Identification of oncogenic microRNA-17–92/ZBTB4/specificity protein axis in breast cancer. Oncogene, 31(8), 1034–1044. 10.1038/onc.2011.296
-
Kozomara, A., Birgaoanu, M. and Griffiths-Jones, S. (2019). miRBase: from microRNA sequences to function. Nucleic acids research, 47(D1), D155-D162. https://doi.org/10.1093/nar/gky1141
-
Lee, R. C., Feinbaum, R. L., Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75(5), 843-854. 10.1016/0092-8674(93)90529-y
-
Li, S., Yang, C., Zhai, L., Zhang, W., Yu, J., Gu, F., Lang, R., Fan, Y., Gong, M., Zhang, X., and Fu, L. (2012). Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast. Breast Cancer Res Treat, 136(1), 77–87. 10.1007/s10549-012-2166-6
-
Li, Y Zhang, L., Dong, Z., Xu, H., Yan, L., Wang, W., Yang, Q., and Chen, C. (2021). MicroRNA-155-5p promotes tumor progression and contributes to paclitaxel resistance via TP53INP1 in human breast cancer. Pathology - Research and Practice, 220, 1-11. https://doi.org/10.1016/j.prp.2021.153405
-
Lima, T. I., Araujo, H. N., Menezes, E. S., Sponton, C.H., Araujo, M. B., Bomfim, L. H. M., Queiroz, A. L., Passos, M. A., Sousa, T. A. E., Hirabara, S. M., Martins, A.R., Sampaio, H. C. L. B., Rodrigues, A., Curi, R., Carneiro, E. M., Boschero, A. C., and Silveira, L. R. (2017). Role of microRNAs on the regulation of mitochondrial biogenesis and insulin signaling in skeletal muscle. Journal of cellular physiology, 232(5), 958-966. 10.1002/jcp.25645
-
Lin, T., Dong, W., Huang, J., Pan, Q., Fan, X., Zhang, C. and Huang, L. (2009). MicroRNA-143 as a tumor suppressor for bladder cancer. The Journal of urology, 181(3), 1372-1380. 10.1016/j.juro.2008.10.149
-
Lu, T. X. and Rothenberg, M. E. (2018). MicroRNA. Journal of Allergy and Clinical Immunology, 141(4), 1202-1207. 10.1016/j.jaci.2017.08.034
-
Lukman Anwar, S., Tanjung, D. S., Fitria, M. S., Kartika, A. I., Indah Sari, D. N., Dinna Rakhmina, D., Wardana, T., Astuti, I., Haryana, S. M., and 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, 21, 491– 497. 10.31557/APJCP.2020.21.2.491
-
Ma, Y., Bu, D., Long, J., Chai, W., and Dong, J. (2019). LncRNA DSCAM-AS1 acts as a sponge of miR-137 to enhance Tamoxifen resistance in breast cancer. Journal of Cellular Physiology, 234(3), 2880–2894. 10.1002/jcp.27105
MacFarlane, L. A., and Murphy, P. R. (2010). MicroRNA: biogenesis, function and role in cancer. Current genomics, 11(7), 537-561. 10.2174/138920210793175895
-
McCaffrey, A. P., Meuse, L., Pham, T. T. T., Conklin, D. S., Hannon, G. J. and Kay, M. A. (2002). RNA interference in adult mice. Nature, 418(6893), 38-39. 10.1038/418038a
-
Meier, J., Hovestadt, V., Zapatka, M., Pscherer, A., Lichter, P., and Seiffert, M. (2013). Genome-wide identification of translationally inhibited and degraded miR-155 targets using RNA-interacting protein-IP. RNA Biology, 10(6), 1017-1029. 10.4161/rna.24553
-
miRBase (2024). World Food Programme, http://mirbase.org/ (Accessed date: 01 March 2025).
-
Mishra, S., Yadav, T., and Rani, V. (2016). Exploring miRNA based approaches in cancer diagnostics and therapeutics. Critical Reviews in Oncology/Hematology, 98, 12–23. http://dx.doi.org/10.1016/j.critrevonc.2015.10.003
-
Mott, J. L., Kobayashi, S., Bronk, S. F. and Gores, G. J. (2007). mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene, 26(42), 6133-6140. 10.1038/sj.onc.1210436
-
Mraz, M., Dolezalova, D., Plevova, K., Kozubik, K. S., Mayerova, V., Cerna, K., Musilova, K., Tichy, B., Pavlova, S., Borsky, M., Verner, J., Doubek, M., Brychtova, Y., Trbusek, M., Hampl, A., Mayer, J., and Pospisilova, S. (2012). MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia. Blood, 119(9), 2110-2113. 10.1038/418038a
-
Musilová, K., and Mráz, M. (2015). MicroRNAs in B-cell lymphomas: how a complex biology gets more complex. Leukemia, 29(5), 1004-1017. 10.1038/leu.2014.351
-
Otmani, K., and Lewalle, P. (2021). Tumor suppressor miRNA in Cancer cells and the tumor microenvironment: mechanism of deregulation and clinical implications. Front. Oncol, 11, 1–15. 10.3389/fonc.2021.708765
-
Rothschild, S. I. (2014). microRNA therapies in cancer. Molecular and cellular therapies, 2(7), 1-8. https://doi.org/10.1186/2052-8426-2-7
-
Saffar, K. N., Larypoor, M. and Torbati, M. B. (2024). Analyzing of colorectal cancerrelated genes and microRNAs expression profiles in response to probiotics Lactobacillus acidophilus and Saccharomyces cerevisiae in colon cancer cell lines. Molecular Biology Reports, 51(1), 1-14. https://doi.org/10.1007/s11033-023-09008-w
-
Salehi, M., Kamali, M. J., Arab, D., Safaeian, N., Ashuori, Z., Maddahi, M., Latifi, N., and Jahromi, A. M. (2024). Exosomal microRNAs in regulation of tumor cells resistance to apoptosis. Biochemistry and Biophysics Reports, 37, 1-14. https://doi.org/10.1016/j.bbrep.2024.101644
-
Smolarz, B., Durczy ´nski, A., Romanowicz, H., Szyłło, K., and Hogendorf, P. (2022). miRNAs in cancer (review of literature). Int. J. Mol. Sci., 23, 1−18. https://doi.org/10.3390/ijms23052805
-
Stankevicins, L., Barat, A., Dessen, P., Vassetzky, Y., and de Moura Gallo, C. V. (2017). The microRNA-205-5p is correlated to metastatic potential of 21T series: A breast cancer progression model. PLoS One, 12(3), e0173756. 10.1371/journal.pone.0173756
-
Takamizawa, J., Konishi, H., Yanagisawa, K., Tomida, S., Osada, H., Endoh, H. and Mitsudomi, T. (2004). Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer research, 64(11), 3753-3756. 10.1158/0008-5472.CAN-04-0637
-
Tan, S., Ding, K., Chong, Q. Y., Zhao, J., Liu, Y., Shao, Y., Yuanyuan Zhang, Y., Yu, Q., Xiong, Z., Zhang, W., Zhang, M., Li, G., Li, X., Kong, X., Ahmad, A., Wu, Z., Wu, Q., Zhao, X., E Lobie, P. E., and Zhu, T. (2017). Post-transcriptional regulation of ERBB2 by miR26a/b and HuR confers resistance to tamoxifen in estrogen receptorpositive breast cancer cells. Journal of Biological Chemistry, 292(33), 13551–13564. 10.1074/jbc.M117.780973
-
Taniguchi, K., Wada, S. I., Ito, Y., Hayashi, J., Inomata, Y., Lee, S. W., Tanaka, T., Komura, K., Akao, Y., Urata, H., and Uchiyama, H. (2019). Tumor α‑aminoisobutyric acid-containing amphipathic helical peptide- cyclic RGD conjugation as a potential drug delivery system for microRNA replacement therapy in vitro. Molecular Pharmaceutics, 16, 4542−4550. 10.3389/fonc.2021.708765
-
Ward, A., Shukla, K., Balwierz, A., Soons, Z., Konig, R., Sahin, O., and Wiemann, S. (2014). MicroRNA-519a is a novel oncomir conferring tamoxifen resistance by targeting a network of tumour-suppressor genes in ER+ breast cancer. The Journal of Pathology, 233(4), 368–379. 10.1002/path.4363
-
Winter, J., Jung, S., Keller, S., Gregory, R. I., and Diederichs, S. (2009). Many roads to maturity: microRNA biogenesis pathways and their regulation. Nature cell biology, 11(3), 228-234. 10.1038/ncb0309-228
-
Wu, Q., Wang, C., Lu, Z., Guo, L., and Ge, Q. (2012). Analysis of serum genome-wide microRNAs for breast cancer detection. Clin. Chim. Acta, 413(13-14), 1058–1065. 10.1016/j.cca.2012.02.016
-
Yang, W., Gu, J., Wang, X., Wang, Y., Feng, M., Zhou, D., Guo, M., and Zhou, M. (2019). Inhibition of circular RNA CDR1as increases chemosensitivity of 5-FU-resistant BC cells through up-regulating miR-7. Journal of Cellular and Molecular Medicine, 23(5), 3166–3177. 10.1111/jcmm.14171
-
Zhang, C. M., Zhao, J., and Deng, H. Y. (2013). MiR-155 promotes proliferation of human breast cancer MCF-7 cells through targeting tumor protein 53-induced nuclear protein 1. Journal of Biomedical Science, 20, 1–10. http://www.jbiomedsci.com/content/20/1/79