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Exploring the Therapeutic Potential of trans-Chalcone: Modulation of MicroRNAs Linked to Breast Cancer Progression in
Tatiana Takahasi Komoto1,2, Felipe Garcia Nishimura1, Adriane Feijó Evangelista3
1Biotechnology Unit, University of Ribeirão Preto, SP, Av. Costábile Romano, 2201, Ribeirão Preto 14096-900, Brazil.
Abstract:
Breast cancer is responsible for 25% of all cancers that affect women. Due to its high heterogeneity pattern in clinical diagnosis and its molecular profile differences, researchers have been seeking new targets and therapies, with more specificity and fewer side effects. Thus, one compound that has garnered our attention is trans-chalcone, which is naturally occurring in various plants and possesses promising biological properties, including antitumor effects. MiRNA is an extensive class of non-coding small, endogenous, and single-stranded RNAs, and it is involved in post-translational gene regulation. Therefore, the objective of this study was to investigate the effects of TChal on miRNAs expression and its relationship with anticancer activity against MCF-7. Initially, the trans-chalcone IC50 value was established by MTT assay for MCF-7and HaCat (non-cancer cell), in which we found out that it was 53.73 and 44.18 μM, respectively. Subsequently, we treated MCF-7 cells with trans-chalcone at its IC50 concentration and performed Mi-seq analysis, which unveiled 23 differentially expressed miRNAs. From this set, we selected five miRNAs (miR-25-5p, miR-27a-3p, miR-891a, miR-449a, and miR-4485) for further validation using qRT-PCR, guided by in silico analysis and their known association with tumorigenesis. In conclusion, our research provides valuable insights into the potential use of TChal to reveal MicroRNAs molecular targets that can be applied in breast cancer therapy.
Insights
Trans-chalcone (TChal) shows anticancer effects against breast cancer cells by altering microRNA (miRNA) expression. This study identified specific miRNAs that could be targeted for novel breast cancer therapies.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Breast cancer is a heterogeneous disease affecting women, necessitating targeted therapies with fewer side effects.
- Naturally occurring compounds like trans-chalcone (TChal) exhibit promising antitumor properties.
- MicroRNAs (miRNAs) are key regulators of gene expression involved in various cellular processes, including cancer development.
Purpose of the Study:
- To investigate the impact of trans-chalcone (TChal) on miRNA expression in breast cancer cells (MCF-7).
- To explore the relationship between TChal-induced miRNA alterations and its anticancer activity.
- To identify potential miRNA targets for breast cancer therapeutic strategies.
Main Methods:
- Determined the IC50 value of trans-chalcone (TChal) in MCF-7 and HaCat cells using MTT assay.
- Performed Mi-seq analysis on MCF-7 cells treated with TChal at IC50 concentration to identify differentially expressed miRNAs.
- Validated the expression of selected miRNAs (miR-25-5p, miR-27a-3p, miR-891a, miR-449a, miR-4485) using qRT-PCR, supported by in silico analysis.
Main Results:
- Trans-chalcone (TChal) exhibited cytotoxic effects on MCF-7 cells with an IC50 of 53.73 μM.
- Mi-seq analysis revealed 23 differentially expressed miRNAs in TChal-treated MCF-7 cells.
- Five specific miRNAs were identified and validated for their altered expression in response to TChal treatment.
Conclusions:
- Trans-chalcone (TChal) modulates miRNA expression in breast cancer cells, contributing to its anticancer effects.
- The identified miRNAs represent potential molecular targets for developing novel breast cancer therapies.
- This research provides a foundation for understanding TChal's mechanism of action and its therapeutic potential in breast cancer.
