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Curcumin plays a leading role as an epigenetic regulator in cancer. miR-15a-5p is a crucial non-coding RNA for breast cancer (BRCA) and various cancers due to its tumor suppressor role. In our study, we aimed to examine the curcumin/miR-15a-5p/target gene interaction in BRCA cells.

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the expression level of the target genes in the cell. Breast cancer is responsible for the majority of cancer-related deaths among women globally. It has been proven that deregulated miRNAs may play an essential role in the progression of breast cancer. It has been shown in many cancers, including breast cancer, that aberrant expression of miRNAs may be associated with drug resistance. This study investigated the effect of let-7b-5p, detected by bioinformatics methods, on Dox resistance through the Aurora Kinase B (AURKB) gene. In silico analysis using publicly available miRNA expression, GEO datasets revealed that let-7b-5p significantly downregulated in BC. Further in silico studies revealed that of the genes among the potential targets of let-7b-5p, AURKB was the most negatively correlated and may be closely associated with Dox resistance. Expression analysis via quantitative PCR confirmed that let-7b-5p was downregulated and AURKB was upregulated in breast cancer tissue samples. Later, functional studies conducted with MCF-10A, MCF-7, and MDA-MB-231 cell lines demonstrated that let-7b-5p inhibits cancer cells through AURKB and sensitizes them to Dox resistance. In conclusion, it has been shown that the let-7b-5p/AURKB axis may be significant in breast cancer progression and the disruption in this axis may contribute to the trigger of Dox resistance. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer (BC) is highly heterogeneous and one of the most common cancers. Luminal A (LUM A) is a subtype of BC with a better prognosis than other BC subtypes. The molecular mechanisms underlying the initiation and progression of the LUM A subtype are still unclear. Big data generated from microarray and sequencing systems can be re-analyzed, especially with the help of various in silico tools developed in recent years, and made applicable for in vitro and in vivo research. This work aimed to identify genes that may play a role in the progression of LUM A subtype of BC using both computational and laboratory-based methods. Materials and Methods: Overlapping genes associated with BC were identified from the The Cancer Genome Atlas database, GSE233242, GSE100925 geodata sets, and the geneshot tool. The network functional analysis between overlapping genes was determined with STRING 12.0. Expression levels of overlapping genes in BC were investigated with the TNMplot (https://tnmplot.com/analysis/) in silico tool. The effect of overlapping genes on the overall survival of LUM A cancer patients was defined using the Kaplan-Meier plotter tool. Expressions of genes identified using bioinformatics data were investigated via quantitative real-time-polymerase chain reaction (qRT-PCR) in LUM A tumor and adjacent tissue samples. The data were evaluated using the t-test. Both the sensitivity and specificity of selected genes have been determined using the receiver operating characteristic curve. Results: In silico investigation showed that eleven genes were possibly associated with BC. Among them CDC25A, AURKB, and TOP2A were considerably increased in LUM A samples according to qRT-PCR results. An overall survival analysis also showed that overexpression of these three genes could reduce the overall survival of LUM A patients. Conclusion: The genes CDC25A, AURKB, and TOP2A may play crucial functions in LUM A pathogenesis. Therapeutic strategies that diminish the expression of these connected genes may enhance the prognosis of LUM A patients. [ABSTRACT FROM AUTHOR]

Objective: Curcumin is considered an epigenetic regulator with anticancer effects. The micro-RNA (miRNA) miR-145-5p is a tumor suppressor that shows low expression levels in various cancers, including breast cancer (BC). This study aims to investigate whether curcumin inhibits MCF-7 human BC cell line proliferation and migration by regulating miR-145-5p and its possible target genes. Material and Method: MCF-7 cells were treated with curcumin and its solvent control. Additionally, cells were transfected with an miR-145-5p mimic and a non-targeting miRNA mimic. Cell viability was then evaluated, and the scratch wound assay was used to assess cell migration. The study predicts the miR-145- 5p putative target genes by searching for overlapping genes in the miRNet and miRTarBase v8 databases via the overexpressed genes in the BC tissue samples in the Cancer Genome Atlas (TCGA) datasets. Expression levels of miR-145-5p and the selected genes were detected using the quantitative real-time polymerase chain reaction (qRT-PCR). The 2-ΔΔCt method was used for the quantification analysis, with p<0.05 being considered statistically significant. Result: Curcumin treatment and overexpression of miR-145- 5p via the transfection of an miR-145-5p mimic significantly decreased the proliferation and migration of MCF-7 cells. Moreover, curcumin treatment significantly increased the expression of miR-145-5p. The possible target genes of miR-145- 5p (i.e., MCM2, MMP1, MMP9, EEF1A2) were downregulated in curcumin-treated MCF-7 cells. Additionally, miR-145-5p mimictransfected cells showed low expression levels of the MCM2, MMP1, and MMP9 genes. Conclusion: Curcumin inhibits the proliferation and migration of MCF-7 cells by acting on miR-145-5p and its possible target genes. [ABSTRACT FROM AUTHOR]