Bioinformatic Prediction of Novel microRNAs Encoded in Krüppel-like Factor 4 Gene

Document Type : Research Article

Authors

1 Farzanegan Campus, Semnan University, Semnan, Iran

2 Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

3 Faculty of Biological Sciences, Semnan University, Semnan, Iran

Abstract

MicroRNAs are small non-coding RNAs that can regulate gene expression that affects various cellular processes. Krüppel-like factor 4 (KLF4) is a transcription factor that has different regulatory functions, and it plays a role in various cellular processes. This study aims to identify novel microRNAs in KLF4 gene using bioinformatics tools. This study significantly contributes to our understanding of the complex function of KLF4 and reveals additional layers of regulatory complexity that affect gene function and cellular dynamics. Advanced bioinformatics methods, including SSCprofiler website, were used to predict stem-loop structures in KLF4 gene, and MatureBayes website was used to predict the mature sequence of microRNAs, which indicate potential miRNA candidates. Using the RNAfold website, the stem-loop structure of microRNAs was determined. The UCSC database assessed the conservation status of these miRNAs and their precursors. From the results of bioinformatics analysis of KLF4 gene, three microRNAs were predicted. Websites and bioinformatics tools were able to predict the sequence of possible microRNAs along with their mature sequence and then depict their stem-loop structure. The analysis of the obtained sequences showed that they are highly conserved, which indicates their importance in the genome. The results obtained in this study show the power and functionality of bioinformatics tools. While the bioinformatic results increase our understanding of the function of the KLF4 gene, experimental studies are needed to confirm these results, which can give us more information about the function of this gene in the future.

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Main Subjects


Blum, A., Mostow, K., Jackett, K., Kelty, E., Dakpa, T., Ryan, C., & Hagos, E. (2021). KLF4 regulates metabolic homeostasis in response to stress. Cells, 10(4), 830. https://doi.org/10.3390/cells10040830
Dokanehiifard, S., Soltani, B. M., Parsi, S., Hosseini, F., Javan, M., & Mowla, S. J. (2015). Experimental verification of a conserved intronic microRNA located in the human TrkC gene with a cell type-dependent apoptotic function. Cellular and Molecular Life Sciences, 72, 2613-2625. https://doi.org/10.1007/s00018-015-1868-4
Dokanehiifard, S., Yasari, A., Najafi, H., Jafarzadeh, M., Nikkhah, M., Mowla, S. J., & Soltani, B. M. (2017). A novel microRNA located in the TrkC gene regulates the Wnt signaling pathway and is differentially expressed in colorectal cancer specimens. Journal of Biological Chemistry, 292(18), 7566-7577. https://doi.org/10.1074/jbc.M116.760710
Ghaleb, A. M., & Yang, V. W. (2017). Krüppel-like factor 4 (KLF4): what we currently know. Gene, 611, 27-37. https://doi.org/10.1016/j.gene.2017.02.025
Hayashi, K., Sasamura, H., Nakamura, M., Azegami, T., Oguchi, H., Sakamaki, Y., & Itoh, H. (2014). KLF4-dependent epigenetic remodeling modulates podocyte phenotypes and attenuates proteinuria. The Journal of Clinical Investigation, 124(6), 2523-2537. https://doi.org/10.1172/jci69557
Kolios, G., & Moodley, Y. (2012). Introduction to stem cells and regenerative medicine. Respiration, 85(1), 3-10. https://doi.org/10.1159/000345615
Krol, J., Loedige, I., & Filipowicz, W. (2010). The widespread regulation of microRNA biogenesis, function and decay. Nature Reviews Genetics, 11(9), 597-610. https://doi.org/10.1038/nrg2843
Li, J. C., Chen, Q. H., Jian, R., Zhou, J. R., Xu, Y., Lu, F., ... & Zhang, H. (2021). The partial role of KLF4 and KLF5 in gastrointestinal tumors. Gastroenterology Research and Practice, 2021. https://doi.org/10.1155/2021/2425356
Lu, T. X., & Rothenberg, M. E. (2018). MicroRNA. Journal of Allergy and Clinical Immunology, 141(4), 1202-1207. https://doi.org/10.1016/j.jaci.2017.08.034
Luo, X., Zhang, Y., Meng, Y., Ji, M., & Wang, Y. (2022). Prognostic significance of KLF4 in solid tumours: an updated meta-analysis. BMC Cancer, 22(1), 181. https://doi.org/10.1186/s12885-022-09198-9
Moreno-Moya, J. M., Vilella, F., & Simón, C. (2014). MicroRNA: key gene expression regulators. Fertility and Sterility, 101(6), 1516-1523. https://doi.org/10.1016/j.fertnstert.2013.10.042
Mullany, L. E., Herrick, J. S., Wolff, R. K., & Slattery, M. L. (2016). MicroRNA seed region length impact on target messenger RNA expression and survival in colorectal cancer. PloS One, 11(4), e0154177. https://doi.org/10.1371/journal.pone.0154177
Park, C. S., Shen, Y., Lewis, A., & Lacorazza, H. D. (2016). Role of the reprogramming factor KLF4 in blood formation. Journal of Leucocyte Biology, 99(5), 673-685. https://doi.org/10.1189/jlb.1RU1215-539R
Parsi, S., Soltani, B. M., Hosseini, E., Tousi, S. E., & Mowla, S. J. (2012). Experimental verification of a predicted intronic microRNA in human NGFR gene with a potential pro-apoptotic function. PloS One, 7(4), e35561. https://doi.org/10.1371/journal.pone.0035561
Quévillon Huberdeau, M., & Simard, M. J. (2019). A guide to micro RNA‐mediated gene silencing. The FEBS Journal, 286(4), 642-652. https://doi.org/10.1111/febs.14666
Saleh, A. J., Soltani, B. M., Dokanehiifard, S., Medlej, A., Tavalaei, M., & Mowla, S. J. (2016). Experimental verification of a predicted novel microRNA located in human PIK3CA gene with a potential oncogenic function in colorectal cancer. Tumor Biology, 37, 14089-14101. https://doi.org/10.1007/s13277-016-5264-y
Simonson, B., & Das, S. (2015). MicroRNA therapeutics: the next magic bullet? Mini Reviews in Medicinal Chemistry, 15(6), 467-474. https://doi.org/10.2174/1389557515666150324123208
Wang, X., Xia, S., Li, H., Wang, X., Li, C., Chao, Y., ... & Han, C. (2020). The deubiquitinase USP10 regulates KLF4 stability and suppresses lung tumorigenesis. Cell Death and Differentiation, 27(6), 1747-1764. https://doi.org/10.1038/s41418-019-0458-7
Yamanaka, S. (2020). Pluripotent stem cell-based cell therapy-promise and challenges. Cell Stem Cell, 27(4), 523-531. https://doi.org/10.1016/j.stem.2020.09.014
Yang, L., Shi, P., Zhao, G., Xu, J., Peng, W., Zhang, J., ... & Cui, H. (2020). Targeting cancer stem cell pathways for cancer therapy. Signal Transduction and Targeted Therapy, 5(1), 8. https://doi.org/10.1038/s41392-020-0110-5
Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: past, present, and future. Stem Cell Research and Therapy, 10(1), 1-22. https://doi.org/10.1186/s13287-019-1165-5
Zeng, Z. L., Lin, X. L., Tan, L. L., Liu, Y. M., Qu, K., & Wang, Z. (2018). MicroRNAs: important regulators of induced pluripotent stem cell generation and differentiation. Stem Cell Reviews and Reports, 14, 71-81. https://doi.org/10.1007/s12015-017-9785-6