Skip to content
Home▶ Journals▶ Applied Biological Research▶Archive▶Vol. 28 No. 3 (2026)▶INTEGRATIVE IDENTIFICATION OF RECURRENT NON-CODING…
Applied Biological Research
Applied Biological Research ›
Print ISSN 0972-0979 · Online ISSN 0974-4517
Submit your paper About the journal
Article

INTEGRATIVE IDENTIFICATION OF RECURRENT NON-CODING MUTATIONS IN MICRORNAs AND TRANSCRIPTION FACTOR BINDING SITES FOR EARLY DETECTION OF PROSTATE CANCER

, , , ,
Amna Amin Sethi — Department of Biomedical Engineering, NED University of Engineering & Technology, LEJ Campus, Karachi – 74800, Sindh (Pakistan)
Faizan Siraj Qureshi — Department of Biomedical Engineering, NED University of Engineering & Technology, LEJ Campus, Karachi – 74800, Sindh (Pakistan)
Syed Fahad Ali — Department of Biomedical Engineering, NED University of Engineering & Technology, LEJ Campus, Karachi – 74800, Sindh (Pakistan)
Haniah Iqbal Naseem — Department of Biomedical Engineering, NED University of Engineering & Technology, LEJ Campus, Karachi – 74800, Sindh (Pakistan)
Tayyaba Wasi — Department of Biomedical Engineering, NED University of Engineering & Technology, LEJ Campus, Karachi – 74800, Sindh (Pakistan)
Published 24 Sep 2026 Vol. 28 No. 3 (2026), pp. 324-334 ● Open access
❝ How to cite 🔗 https://doi.org/10.48165/abr.2026.28.01.33
Formats:PDF ● Open access
Download PDF

Abstract

Prostate cancer remains a major global health challenge, and the largely  unexplored non-coding genome—including microRNAs (miRNAs) and  transcription factor binding sites (TFBS) — offers critical insights into its early  molecular events. This study is distinct in integration of computational analyses  of both TFBS and miRNAs to identify highly recurrent mutations within non coding regions of prostate cancer. Point mutations were retrieved from the  COSMIC database and then subjected to computational analysis. Recurrent  non-coding mutations were identified in MIR100HG, MIR4432, and MIR2054.  These statistically significant mutations were mapped to prostate cancer cell-line  specific TFBS, revealing their presence within recurrent mutational hotspots.  Importantly, a 10,000-bootstrap randomization model (q < 0.05) confirmed that  these hotspots are unlikely to be random. The loci identified here represent strong candidate regulatory regions that warrant experimental validation  through approaches like luciferase reporter assays, and CRISPR-based editing, aswell as clinical cohort studiesto establish their functional and causalrelevance. Overall,thisframeworkhighlights coordinateddisruptionsacrosstranscriptional   and post-transcriptional networks, offering a novel computational strategy to  distinguish biologically meaningful regulatory loci from background genetic  noise. By doing so, it provides a foundation for future biomarker discovery and  the development of targeted interventions in prostate cancer. 

 

KeywordsCell linesmicroRNAsprostate cancerrecurrent non-coding mutationstranscription factor binding sites

The full text of this article is available as a PDF.

Download PDF
  1. Abubakar, M., & Rehman, B. (2024). Roles of mutant TP53 gene in cancer development and progression. Proceedings of Anticancer Research, 8(5), 165–181.
  2. Ahmadi, S. E., Rahimi, S., Zarandi, B., Chegeni, R., & Safa, M. (2021). MYC: A multipurpose oncogene with prognostic and therapeutic implications in blood malignancies. Journal of Hematology & Oncology, 14(1), 121. https://doi.org/10.1186/s13045-021-01111-4
  3. Akhtar, S., Hassan, F., Ahmad, S., El-Affendi, M. A., & Khan, M. I. (2023). The prevalence of prostate cancer in Pakistan: A systematic review and meta-analysis. Heliyon, 9(10), e20350. https://doi.org/10.1016/j.heliyon.2023.e20350
  4. Bu, T., Li, L., & Tian, J. (2023). Unlocking the role of non-coding RNAs in prostate cancer progression: Exploring the interplay with the Wnt signaling pathway. Frontiers in Pharmacology, 14, 1269233. https://doi.org/10.3389/fphar.2023.1269233
  5. Castro-Mondragon, J. A., Aure, M. R., Lingjærde, O. C., Langerød, A., Martens, J. W. M., Børresen-Dale, A. L., et al. (2022). Cis-regulatory mutations associate with transcriptional and post-transcriptional deregulation of gene regulatory programs in cancers. Nucleic Acids Research, 50(21), 12131–12148.
  6. Cussenot, O., Cancel-Tassin, G., Rao, S. R., Woodcock, D. J., Lamb, A. D., Mills, I. G., et al. (2023). Aligning germline and somatic mutations in prostate cancer. Are genetics changing practice? BJU International, 132(5), 472–484.
  7. Dai, M., Shi, Y., Zhao, H., Hu, Y., Cong, X., Yu, B., et al. (2025). A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer. Cell Communication and Signaling, 23(1), 328. https://doi.org/10.1186/s12964-025-02280-2
  8. Fatemeh, S., Mahboobeh, Z., Khadijeh, A., Amirhossein, M. K., & Pegah, M. (2024). An in silico study to determine susceptibility to cancer by evaluating the coding and non-coding non-synonymous single nucleotide variants in the SOCS3 gene. Journal of Biomolecular Structure and Dynamics, 42(16), 8281–8292.
  9. Gammall, J., & Lai, A. G. (2024). Prognostic determinants in cancer survival: A multidimensional evaluation of clinical and genetic factors across 10 cancer types in the participants of Genomics England’s 100,000 Genomes Project. Discover Oncology, 15(1), 448. https://doi.org/10.1007/s12672-024-01310-8
  10. Goztepe, M., & Eroglu, O. (2024). Research of the unrecognised functions of miR-375 in prostate cancer cells. Cellular and Molecular Biology, 70(3), 212–218.
  11. Gschwind, A. R., Mualim, K. S., Karbalayghareh, A., Sheth, M. U., Dey, K. K., Jagoda, E., et al. (2023). An encyclopedia of enhancer-gene regulatory interactions in the human genome. bioRxiv. https://doi.org/10.1101/2023.11.09.563812
  12. Gujrati, H., Ha, S., & Wang, B. D. (2023). Deregulated microRNAs involved in prostate cancer aggressiveness and treatment resistance mechanisms. Cancers, 15(12), 3140. https://doi.org/10.3390/cancers15123140
  13. Handler, J. S., Li, Z., Dveirin, R. K., Fang, W., Goodarzi, H., Fertig, E. J., et al. (2024). Identifying a gene signature of metastatic potential by linking the pre-metastatic state to ultimate metastatic fate. bioRxiv. https://doi.org/10.1101/2024.08.14.607813
  14. He, Y., Xu, W., Xiao, Y. T., Huang, H., Gu, D., & Ren, S. (2022). Targeting signaling pathways in prostate cancer: Mechanisms and clinical trials. Signal Transduction and Targeted Therapy, 7(1), 198. https://doi.org/10.1038/s41392-022-01042-7
  15. Iñiguez-Muñoz, S., Llinàs-Arias, P., Ensenyat-Mendez, M., Bedoya-López, A. F., Orozco, J. I. J., Cortés, J., et al. (2024). Hidden secrets of the cancer genome: Unlocking the impact of non-coding mutations in gene regulatory elements. Cellular and Molecular Life Sciences, 81(1), 274. https://doi.org/10.1007/s00018-024-05314-z
  16. Kulac, I., Roudier, M. P., & Haffner, M. C. (2024). Molecular pathology of prostate cancer. Clinics in Laboratory Medicine, 44(2), 161–180.
  17. Morova, T., McNeill, D. R., Lallous, N., Gönen, M., Dalal, K., Wilson, D. M., et al. (2020). Androgen receptor-binding sites are highly mutated in prostate cancer. Nature Communications, 11(1), 832. https://doi.org/10.1038/s41467-020-14644-y
  18. Nourbakhsh, M., Degn, K., Saksager, A., Tiberti, M., & Papaleo, E. (2024). Prediction of cancer driver genes and mutations: The potential of integrative computational frameworks. Briefings in Bioinformatics, 25(2), bbad519. https://doi.org/10.1093/bib/bbad519
  19. Peng, Y., Song, W., Teif, V. B., Ovcharenko, I., Landsman, D., & Panchenko, A. R. (2024). Detection of new pioneer transcription factors as cell-type-specific nucleosome binders. eLife, 12, RP88936. https://doi.org/10.7554/eLife.88936
  20. Rana, S., Valbuena, G. N., Curry, E., Bevan, C. L., & Keun, H. C. (2022). MicroRNAs as biomarkers for prostate cancer prognosis: A systematic review and a systematic reanalysis of public data. British Journal of Cancer, 126(3), 502–513.
  21. Ren, S., Li, J., Dorado, J., Sierra, A., González-Díaz, H., Duardo, A., et al. (2023). From molecular mechanisms of prostate cancer to translational applications: Based on multi-omics fusion analysis and intelligent medicine. Health Information Science and Systems, 12(1), 6. https://doi.org/10.1007/s13755-023-00264-5
  22. Saha, D., Dang, H. X., Zhang, M., Quigley, D. A., Feng, F. Y., & Maher, C. A. (2024). Single cell transcriptomic analysis informs the lncRNA landscape in metastatic castration-resistant prostate cancer. NPJ Genomic Medicine, 9(1), 14. https://doi.org/10.1038/s41525-024-00401-3
  23. Schitcu, V. H., Raduly, L., Nutu, A., Zanoaga, O., Ciocan, C., Munteanu, V. C., et al. (2022). MicroRNA dysregulation in prostate cancer. Pharmacogenomics and Personalized Medicine, 15, 177–193.
  24. Sethi, A. A., & Shar, N. A. (2023). Identification of liver cancer driver mutations from COSMIC data. International Journal of Cancer Management, 16(1), e131281. https://doi.org/10.5812/ijcm.131281
  25. Singh, V. K., Rajak, N., Singh, Y., Singh, A. K., Giri, R., & Garg, N. (2024). Role of microRNA-21 in prostate cancer progression and metastasis: Molecular mechanisms to therapeutic targets. Annals of Surgical Oncology, 31(7), 4795–4808.
  26. Taheri, M., Badrlou, E., Hussen, B. M., Kashi, A. H., Ghafouri-Fard, S., & Baniahmad, A. (2023). Importance of long non-coding RNAs in the pathogenesis, diagnosis, and treatment of prostate cancer. Frontiers in Oncology, 13, 1123101. https://doi.org/10.3389/fonc.2023.1123101
  27. Tang, Q., Zuo, W., Wan, C., Xiong, S., Xu, C., Yuan, C., et al. (2023). Comprehensive genomic profiling of upper tract urothelial carcinoma and urothelial carcinoma of the bladder identifies distinct molecular characterizations with potential implications for targeted therapy and immunotherapy. Frontiers in Immunology, 13, 1097730. https://doi.org/10.3389/fimmu.2022.1097730
  28. Vattathil, S. M., Gerasimov, E. S., Canon, S. M., Lori, A., Tan, S. S. M., Kim, P. J., et al. (2025). Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions. Nature Aging, 5(2), 306–319.
  29. Wakeley, J., Fan, W. L., Koch, E., & Sunyaev, S. (2023). Recurrent mutation in the ancestry of a rare variant. Genetics, 224(3), iyad049. https://doi.org/10.1093/genetics/iyad049
  30. Wang, Z., Luo, M., Liang, Q., Zhao, K., Hu, Y., Wang, W., et al. (2023). Landscape of enhancer disruption and functional screen in melanoma cells. Genome Biology, 24(1), 248. https://doi.org/10.1186/s13059-023-03087-5
  31. Woo, B. J., Moussavi-Baygi, R., Karner, H., Karimzadeh, M., Yousefi, H., Lee, S., et al. (2024). Integrative identification of non-coding regulatory regions driving metastatic prostate cancer. Cell Reports, 43(9), 114764. https://doi.org/10.1016/j.celrep.2024.114764
  32. Xiang, Z., Lin, T., Ling, J., Xu, Z., Huang, R., & Hu, H. (2025). MiRNA expression profiling and clinical implications in prostate cancer across various stages. Scientific Reports, 15(1), 7771. https://doi.org/10.1038/s41598-025-92091-9
  33. Xie, H., Chen, J., Ma, Z., Gao, Y., Zeng, J., Chen, Y., et al. (2024). PrLZ regulates EMT and invasion in prostate cancer via the TGF-β1/p-Smad2/miR-200 family/ZEB1 axis. Prostate, 84(4), 317–328.
  34. Yuan, S., Ni, P., & Su, Z. (2025). Prediction of target genes and functional types of cis-regulatory modules in the human genome reveals their distinct properties. BMC Biology, 23(1), 211. https://doi.org/10.1186/s12915-025-02313-9
  35. Zhou, H., Hao, X., Zhang, P., & He, S. (2023). Noncoding RNA mutations in cancer. Wiley Interdisciplinary Reviews: RNA, 14(6), e1812. https://doi.org/10.1002/wrna.1812
  36. Zhou, S., Hawley, J. R., Soares, F., Grillo, G., Teng, M., Madani Tonekaboni, S. A., et al. (2020). Noncoding mutations target cis-regulatory elements of the FOXA1 plexus in prostate cancer. Nature Communications, 11(1), 441. https://doi.org/10.1038/s41467-020-14318-9

Looking up citing articles…