Abstract
Background
Cancer bladder is the most common malignant tumor affecting the urinary tract. Genetic alterations are tightly associated with the development of cancer bladder. MicroRNAs (miRNA) are small, noncoding single-stranded RNA molecules that have been linked to bladder cancer. miR-124-3pa exhibits altered expression in various types of human malignancies. DNA methyltransferase 3B (DNMT3B) is responsible for de novo DNA methylation which is a fundamental epigenetic process in carcinogenesis. This work was performed to study the expression of DNMT3B and miR 124-3pa in bladder cancer tissues, and investigate their significance in the diagnosis and prognosis of the disease.
Subjects & methods
This case-control study included one hundred and six tissue samples of patients with primary urothelial bladder cancer. The tissues were separated into two parts. The first part was immediately frozen and kept at − 80 °C for total RNA extraction with subsequent detection of miR 124-3pa and DNMT3B expressions. The other part was preserved in formalin solution for histopathological examination.
Results
There was a highly statistically significant difference between the cancerous and the normal tissues as regarding miRNA-124-3pa and DNMT3B expression (P < 0.001) for each. Also, there was a highly statistically significant strong negative correlation between miRNA-124-3pa and DNMT3B expression (r=-0.750, P < 0.001). The combined performance of miR-124-3pa and DNMT3B revealed that the cutoff point of ≥ 3.3 can be used as a predictor of the presence of cancer bladder with sensitivity of 98.1% and specificity of 80%.
Conclusion
miR-124-3pa and DNMT3B can be used as predictors of the presence of cancer bladder.
Similar content being viewed by others
Data Availability
Available upon a reasonable request.
References
Madej A, Forma E, Golberg M et al (2022) 13 C natural isotope abundance in Urothelium as a new marker in the Follow-Up of patients with bladder Cancer. Cancers 14(10):2423
Gaber DA, Wassef RM, El-Ayat WM et al (2020) Role of a schistosoma haematobium specific microRNA as a predictive and prognostic tool for bilharzial bladder cancer in Egypt. Sci Rep 10(1):1–10
Flaig TW, Spiess PE, Agarwal N et al (2020) Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 18(3):329–354
Lobo N, Afferi L, Moschini M et al (2022) Epidemiology, screening, and Prevention of bladder Cancer. European Urology Oncology
Chen L, Liu Y, Zhang Q et al (2019) p53/PCDH17/Beclin-1 proteins as prognostic predictors for urinary bladder cancer. J Cancer 10(25):6207
Slovacek H, Zhuo J, Taylor JM (2021) Approaches to Non-MuscleInvasive bladder Cancer. Curr Oncol Rep 23(9):1–11
Pozniak T, Shcharbin D, Bryszewska M (2022) Circulating microRNAs in Medicine. Int J Mol Sci 23(7):3996
Zhu Q, Zhang Y, Li M et al (2023) MiR-124-3p impedes the metastasis of non-small cell lung cancer via extracellular exosome transport and intracellular PI3K/AKT signaling. Biomark Res 11(1):1–17
Hsu FT, Liu WL, Lee SR, Jeng LB, Chen JH (2023) Unveiling nature’s potential weapon: Magnolol’s role in combating bladder cancer by upregulating the miR-124 and inactivating PKC-δ/ERK axis. Phytomedicine 119:154947. https://doi.org/10.1016/j.phymed.2023.154947Epub 2023 Jul 26. PMID: 37549536
Bhootra S, Jill N, Shanmugam G, Rakshit S, Sarkar K (2023) DNA methylation and cancer: transcriptional regulation, prognostic, and therapeutic perspective. Med Oncol 40(2):1–17
Loaeza-Loaeza J, Cerecedo-Castillo AJ, Rodríguez-Ruiz HA et al (2022) DNMT3B overexpression downregulates genes with CpG islands, common motifs, and transcription factor binding sites that interact with DNMT3B. Sci Rep 12(1):1–13
Peres R, Furuya H, Pagano I, Shimizu Y, Hokutan K, Rosser CJ (2016) Angiogenin contributes to bladder cancer tumorigenesis by DNMT3b-mediated MMP2 activation. Oncotarget 7(28):43109–43123. https://doi.org/10.18632/oncotarget.10097PMID: 27317771; PMCID: PMC5190012
Ying Y, Li J, Xie H, Yan H, Jin K, He L, Ma X, Wu J, Xu X, Fang J, Wang X, Zheng X, Liu B, Xie L (2020) CCND1, NOP14 and DNMT3B are involved in mir-502-5p-mediated inhibition of cell migration and proliferation in bladder cancer. Cell Prolif 53(2):e12751. https://doi.org/10.1111/cpr.12751Epub 2020 Jan 23. PMID: 31971654; PMCID: PMC7048215
Pal A (2022) Real-time or quantitative PCR. Protocols in Advanced Genomics and Allied Techniques. Springer, New York, NY, pp 181–209
Al-Sabaawy HB, Rahawi AM, Al-Mahmood SS (2021) Standard techniques for formalin-fixed paraffin-embedded tissue: a pathologist’s perspective. Iraqi J Veterinary Sci 35:127–135
Zhang W, He X, Yin H et al (2022) Allosteric activation of the metabolic enzyme GPD1 inhibits bladder cancer growth via the lysoPC-PAFR-TRPV2 axis. J Hematol Oncol 15(1):1–17
Wigner P, Grębowski R, Bijak M, Saluk-Bijak J, Szemraj J (2021) The interplay between oxidative stress, inflammation and angiogenesis in bladder cancer development. Int J Mol Sci 22(9):4483
Tran L, Xiao JF, Agarwal N, Duex JE, Theodorescu D (2021) Advances in bladder cancer biology and therapy. Nat Rev Cancer 21(2):104–121
Uzuner E, Ulu GT, Gürler SB, Baran Y (2022) The role of MiRNA in cancer: pathogenesis, diagnosis, and treatment. miRNomics. Humana, New York, NY, pp 375–422
Yang X, Wang J, Li H, Sun Y, Tong X (2021) Downregulation of hsa_circ_0026123 suppresses ovarian cancer cell metastasis and proliferation through the miR-124-3p/EZH2 signaling pathway. Int J Mol Med 47(2):668–676
Zhu B, Cui H, Xu W (2021) Hydrogen inhibits the proliferation and migration of gastric cancer cells by modulating lncRNA MALAT1/miR-124-3p/EZH2 axis. Cancer Cell Int 21(1):1–10
Memari F, Tavakolpour V, Mohajeri N et al (2022) Distinct power of bone marrow microRNA signatures and tumor suppressor genes for early detection of acute leukemia. Clin Transl Oncol, 1–9
Alshammari E, Zhang Y, Sobota J, Yang Z (2022) Aberrant DNA methylation of Tumor suppressor genes and oncogenes as Cancer biomarkers. Genomic and Epigenomic Biomarkers of Toxicology and Disease: Clinical and Therapeutic Actions, 251–271
Flausino CS, Daniel FI, Modolo F (2021) DNA methylation in oral squamous cell carcinoma: from its role in carcinogenesis to potential inhibitor drugs. Crit Rev Oncol/Hematol 164:103399
Viswambaram P, Hayne D (2020) Gender discrepancies in bladder cancer: potential explanations. Expert Rev Anticancer Ther 20(10):841–849
Martin A, Woolbright BL, Umar S, Ingersoll MA, Taylor JA (2022) Bladder cancer, inflammageing and microbiomes. Nat Reviews Urol 19(8):495–509
Yuan Q, Sun T, Ye F, Kong W, Jin H (2017) MicroRNA-124-3p affects proliferation, migration and apoptosis of bladder cancer cells through targeting AURKA. Cancer Biomarkers 19(1):93–101
Wang S, Wu G, Han Y et al (2018) miR-124 regulates STAT3-mediated cell proliferation, migration and apoptosis in bladder cancer. Oncol Lett 16(5):5875–5881
Cao Z, Xu L, Zhao S, Zhu X (2019) The functions of microRNA-124 on bladder cancer. OncoTargets and Therapy 12:3429
Fu W, Wu X, Yang Z, Mi H (2019) The effect of mir-124-3p on cell proliferation and apoptosis in bladder cancer by targeting EDNRB. Archives of Medical Science: AMS 15(5):1154
Wang JR, Liu B, Zhou L, Huang YX (2019) MicroRNA-124-3p suppresses cell migration and invasion by targeting ITGA3 signaling in bladder cancer. Cancer Biomarkers 24(2):159–172
Awadalla A, Abol-Enein H, Hamam ET et al (2022) Identification of epigenetic interactions between miRNA and gene expression as potential prognostic markers in bladder Cancer. Genes 13(9):1629
Ge Q, Lu M, Ju L et al (2019) Mir-4324‐RACGAP1‐STAT3‐ESR1 feedback loop inhibits proliferation and metastasis of bladder cancer. Int J Cancer 144(12):3043–3055
Xu K, Chen B, Li B et al (2020) DNMT3B silencing suppresses migration and invasion by epigenetically promoting miR-34a in bladder cancer. Aging 12(23):23668
Ying Y, Li J, Xie H et al (2020) CCND1, NOP14 and DNMT3B are involved in miR-502‐5p–mediated inhibition of cell migration and proliferation in bladder cancer. Cell Prolif, 53(2), e12751
Zo RB, Long Z (2019) MiR-124‐3p suppresses bladder cancer by targeting DNA methyltransferase 3B. J Cell Physiol 234(1):464–474
Cao Y, Xu K, Chen B et al (2020) Expression of DNMT3b in human bladder cancer tissue and its correlation with clinical prognosis. Nan Fang yi ke da xue xue bao = Journal of Southern Medical University 40(9):1295–1300
Li R, Chen X, Li X et al (2022) A four-miRNA signature in serum as a biomarker for bladder cancer diagnosis. Am J Translational Res 14(7):4606
Acknowledgements
Not applicable.
Funding
>Not applicable.
Author information
Authors and Affiliations
Contributions
MSF, ARME, and SH designed and directed the project. SH and AMZE performed the experiments, analyzed the data, and wrote the manuscript which was revised by all co-authors.
Corresponding author
Ethics declarations
Conflict of interest
None.
Competing interests
The authors declare no competing interests.
Ethics approval and consent to participate
The study protocol was approved by the Institute Review Board of the Faculty of Medicine, Zagazig University (ZU-IRB#9014/25-10-2021).
Consent for publication
Not applicable.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Fawzy, M.S., El Faiomy, A.R.M., El Desoky, A.M.Z. et al. The relationship between DNA methyltransferase 3B (DNMT3B) and miR 124-3pa expressions in bladder cancer tissues. Mol Biol Rep 50, 10005–10013 (2023). https://doi.org/10.1007/s11033-023-08818-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-023-08818-2