Genistein Exerts Anti-proliferative Effects by Regulating Apoptosis and Autophagy-Related Genes and MicroRNAs in Human Urinary Bladder Neoplasm EJ138 Cells: An Experimental and Bioinformatic Study

AuthorAlireza Ziyabakhshen
AuthorMohammad Amin Vatankhahen
AuthorFarid Pakizehen
AuthorAli Nosraten
AuthorPouria Sobhien
AuthorMohammad Vakili Ojarooden
AuthorSina Seifimansouren
OrcidAlireza Ziyabakhsh [0000-0003-4724-0901]en
OrcidMohammad Amin Vatankhah [0000-0002-8855-6614]en
OrcidFarid Pakizeh [0009-0005-2268-4954]en
OrcidAli Nosrat [0009-0008-0642-0520]en
OrcidMohammad Vakili Ojarood [0000-0002-4396-5828]en
OrcidSina Seifimansour [0009-0000-4410-1741]en
Issued Date2025-12-31en
AbstractBackground: Bladder cancer (BC) is the most prevalent urogenital malignancy. Recently, the combination of natural compounds with chemotherapeutic agents has gained attention. Genistein, a natural flavonoid, exhibits anti-cancer properties and represents a promising candidate for treating various cancerous cells due to its cytotoxic potential and minimal adverse effects. Objectives: This study aimed to evaluate the anti-cancer effects of genistein by regulating potential target genes and microRNAs involved in apoptosis and autophagy in EJ138 BC cells. Methods: EJ138 BC cells were treated with different concentrations of genistein, and cell viability was assessed using the MTT assay. To determine the apoptotic rate of EJ138 BC cells following genistein treatment, flow cytometry with Annexin V/PI staining was performed. Additionally, real-time PCR was conducted to analyze the expression of miR-27a, miR-151, apoptotic genes (caspase-3, caspase-9), and autophagic genes (ATG12, Beclin1) after 48 hours of genistein treatment. Statistical analysis was carried out using SPSS V.22, with independent t-tests and one-way ANOVA. Results were considered statistically significant at P < 0.05. Results: Our findings demonstrated that genistein inhibited the proliferation, growth, and viability of EJ138 BC cells and induced cell death. Real-time PCR results confirmed that genistein significantly upregulated miR-27a (P < 0.01), ATG12 (P < 0.01), Beclin1 (P < 0.05), caspase-3 (P < 0.001), and caspase-9 (P < 0.0001), while downregulating miR-151 expression (P < 0.05). Conclusions: The results of this study suggest that genistein suppresses the proliferation and growth of human BC cells by modulating genes and microRNAs involved in apoptosis and autophagy. Therefore, genistein may serve as a novel therapeutic agent for BC treatment.en
DOIhttps://doi.org/10.5812/ijpr-157853en
KeywordUrinary Bladder Neoplasmsen
KeywordGenisteinen
KeywordApoptosisen
KeywordAutophagyen
KeywordMicroRNAsen
PublisherBrieflandsen
TitleGenistein Exerts Anti-proliferative Effects by Regulating Apoptosis and Autophagy-Related Genes and MicroRNAs in Human Urinary Bladder Neoplasm EJ138 Cells: An Experimental and Bioinformatic Studyen
TypeResearch Articleen

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