Therapeutic targeting of triple-negative breast cancer: A multi-model evaluation of LNA-anti-miR-19b-3p and small molecule inhibitors

• Published in: Computers in biology and medicine Vol. 196; no. Pt A; p. 110771
• Main Authors: Kamali, Mohammad Javad, Saeedi, Fatemeh, Khoshghiafeh, Azin, Mir, Mahsa Aghajani, Aram, Cena, Ahmadifard, Mohamadreza
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.09.2025
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic - drug effects; Hsa-miR-19b-3p; Humans; Internal Medicine; Locked nucleic acid; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular docking; Oligonucleotides - genetics; Oligonucleotides - pharmacology; Other; Therapy; TNBC; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Therapy; Hsa-miR-19b-3p; TNBC; Locked nucleic acid; Molecular docking
• ISSN: 0010-4825; 1879-0534; 1879-0534
• DOI: 10.1016/j.compbiomed.2025.110771

The potential of inhibiting hsa-miR-19b-3p as a therapeutic approach for triple-negative breast cancer (TNBC) was investigated. To explore this, we studied the function of hsa-miR-19b-3p in TNBC cells, specifically the MDA-MB-231 cell line. We transfected these cells with LNA-anti-miR to inhibit the miRNA and then used qRT-PCR to measure the level of inhibition. Interestingly, we observed over 95 % inhibition at 24 h, and even at 48 h, the inhibition remained high at over 75 %. Upon closer examination, we determined the impact of this inhibition on cell viability using MTT assays, which showed a significant decrease in cell numbers following treatment with LNA-anti-miR-19b-3p. Furthermore, our apoptosis analysis, using Annexin V/Propidium iodide staining, revealed an increased apoptosis rate in the transfected cells compared to the controls. Alongside these experimental studies, we employed computational methods to investigate hsa-miR-19b-3p in greater detail, including RNA-Seq analysis of TCGA data, which identified 2585 upregulated and 4251 downregulated genes. Cross-referencing downregulated genes with target genes from miRTarBase, RNAInter, and miRWalk led to the identification of four potential hsa-miR-19b-3p targets: TMTC1, MBNL3, FAT3, and GFOD1, with TMTC1 and MBNL3 showing statistically significant downregulation. Additionally, we screened for potential small molecule inhibitors, identifying four promising candidates, including Dovitinib, S-Adenosylmethionine, Guanosine-5′,3′-tetraphosphate, and Neomycin, which exhibited favorable drug-like characteristics. In conclusion, our multifaceted approach demonstrates the significant potential of LNA-anti-miR-19b-3p as a therapeutic option for TNBC patients, and the small molecule inhibitors we've uncovered could open new avenues for treating this aggressive form of breast cancer. [Display omitted] •Hsa-miR-19b-3p inhibition shows potential for triple-negative breast cancer therapy.•LNA-anti-miR transfection achieved over 95 % inhibition in TNBC cells within 24 h.•Significant reduction in cell viability and increased apoptosis observed post-treatment.•Four small molecule inhibitors identified as potential therapeutic candidates for TNBC.