Recent research suggests curcumin extracted from the turmeric plant may inhibit the proliferation of cancer cells by controlling the expression of microRNAs (miRNAs). The effect of phenolic curcumin on miR-638-5p and potential target gene expressions in the triple negative breast cancer (TNBC) cell line MDA-MB-231 was investigated in this study. GSE154255 and GSE40525 datasets were downloaded and analyzed using GEO2R to identify dysregulated miRNAs in TNBC. To find differently expressed genes in breast cancer (BRCA), The Cancer Genome Atlas Program data was examined. Utilizing in silico tools, KEGG, GO, and other enrichment analyses were performed. The databases miRNet, miRTarBase v8.0, and TarBase v.8 were used for miRNA and mRNA matching. Real-time quantitative reverse transcription polymerase chain reaction was used to examine the levels of miRNA and its targets in miRNA mimic transfected/curcumin-treated MDA-MB-231 cultures and controls. The cell viability detection kit-8 method was used to assess cell viability, and the scratch assay was used to conduct migration assessment. Bioinformatics analysis showed that miR-638-5p was significantly reduced in TNBC patients. Experimental results showed that miR-638-5p was upregulated in MDA-MB-231 treated with curcumin, while the potential target genes of miR-638-5p, CFL1, SIX4, MAZ, and CDH1 were downregulated. Mimic miR-638-5p transfection inhibited MDA-MB-231 cell proliferation and reduced migration and expression of CFL1, SIX4, and MAZ genes was decreased in mimic miR-638-5p transfected cells. These findings suggest that curcumin exerts its anticancer effects on MDA-MB-231 cells by modulating the expression of miR-638-5p and its possible target genes.

Overexpression of CDC25A, AURKB, and TOP2A Genes Could Be an Important Clue for Luminal A Breast Cancer - European Journal of Breast Health

Background: Carvacrol, a natural phenolic monoterpenoid, has been suggested to exert anticancer effects; however, its underlying mechanisms in breast cancer (BC) remain incompletely defined. Methods: MCF-7 (HR⁺) and MDA-MB-231 (TNBC) BC cell lines were treated with carvacrol at various concentrations. Cell viability was assessed using CVDK8 kit, while migration was evaluated by wound healing assays. Apoptosis was determined using Annexin V-FITC Kit, and ROS levels were measured by DCFH-DA assay. Flow cytometry was used for CD44/CD133 cancer stem cells markers analysis, and genes expression were quantified using qPCR. Results: Carvacrol significantly inhibited cell proliferation, and migration in both HR⁺ and TNBC cells. Additionally, carvacrol increased the BAX/BCL2 ratio, induced apoptosis, and decreased ROS levels, with greater antioxidant activity observed in MCF-7 cells. Moreover, carvacrol suppressed CD44⁺ levels, whereas CD133⁺ levels were not affected. Gene expression analysis revealed subtype-specific effects where ABCG2 was upregulated in MCF-7 cells but downregulated in MDA-MB-231 cells, while NF_KB1 expression increased in both lines. Conclusions: Carvacrol exerts multitargeted anticancer effects in BC by promoting apoptosis, reducing ROS, and suppressing CD44⁺, with distinct subtype-specific responses. These findings highlight carvacrol as a promising natural therapeutic compound for BC treatment; however, further in vivo studies and clinical investigations are required to validate its translational potential.

Objectives: 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. Methods: The effects of curcumin and miR-15a-5p on cell viability in the MCF7 cells were examined using the WST8 technique. The cell migration was determined using scratch wound assay. miR-15a-5p level was detected in curcumin-treated cells and miR-15a-5p transfected cells compared to control groups by RT-qPCR. Overexpressed genes in BRCA were found by bioinformatics tools (GSE41970 and TCGA). miR15a-5p potential target genes in the miRNet tool were selected in overlapped genes between GSE41970 and TCGA. Survival analysis of the selected genes was examined using the GEPIA2 tool. Relative expression levels of four selected genes were examined via qPCR. Results: Cell viability and scratch-wound closure rate were reduced in curcumin-treated and miR-15a-5p mimic transfected MCF7 cells. miR15a-5p overexpressed in curcumin-treated and miR-15a-5p transfected cells. Eighty-three dysregulated upregulated genes were detected (in GSE41970 and TCGA). Among the possible target genes of miR-15a-5p in the miRNet tool, 10 upregulated genes were detected overlapping with GSE41970 and TCGA. CCNE1 and CHEK1 genes were found to be important for survival in BRCA. CCNE1 and BMI1 were decreased in curcumin-treated and miR-15a-5p transfected cells. Conclusions: Curcumin treatment increased miR-15a-5p and downregulated selected target genes. Curcumin/miR-15a-5p interaction may be a much stronger negative regulator of the CCNE1 and BMI1 genes in BRCA.

Objective: Tubular breast carcinoma (TBC) is a rare subtype of breast carcinoma (BC) with a good prognosis. In this study, we aimed to assess the clinicopathological characteristics of pure TBC (PTBC), analyze factors that may influence long-term prognosis, examine the frequency of axillary lymph node metastasis (ALNM), and discuss the need for axillary surgery in PTBC.Materials and Methods: Fifty-four Patients diagnosed with PTBC between January 2003 and December 2020 at Istanbul Faculty of Medicine were included. Clinicopathological, surgical, treatment, and overall survival (OS) data were analyzed.Results: A total of 54 patients with a mean age of 52.2 years were assessed. The mean size of the tumor was 10.6 mm. Four (7.4%) patients had not undergone axillary surgery, while thirty-eight (70.4%) had undergone sentinel lymph node biopsy and twelve (22.2%) had undergone axillary lymph node dissection (ALND). Significantly, four (33.3%) of those who had undergone ALND had tumor grade 2 (p = 0.020) and eight of them (66.7%) had ALNM. Fifty percent (50%) of patients who were treated with chemotherapy had grade 2 and multifocal tumors and ALNM. Moreover, the frequency of ALNM was higher in patients with tumor diameters greater than 10 mm. Median follow-up time was 80 months (12-220). None of the patients had locoregional recurrence, but one patient had systemic metastasis. Furthermore, five-year OS was 97.9%, while ten-year OS was 93.6%.Conclusion: PTBC is associated with favorable prognosis, good clinical outcomes and high survival rate, with rare recurrences and metastases.

Background and Objectives: Curcumin is a turmeric-derived polyphenol, and it has shown anticancer potential in various cancers, including breast cancer (BC). Nevertheless, the molecular mechanisms underlying its effects remain incompletely defined. Hsa_circ_0001946 (CDR1as) is a circular RNA (circRNA) that promotes tumor progression by competitively inhibiting microRNA-7-5p (miR-7-5p) in BC. This study investigated whether curcumin regulates the hsa_circ_0001946/miR-7-5p/target gene axis in BC progression. Materials and Methods: BC cell lines (MCF-7 and T47D) and a non-cancerous human mammary epithelial cell line (MCF-10A) were treated with curcumin or transfected with circ_0001946 siRNA or miR-7-5p mimic. Cell proliferation, migration, apoptosis, and protein expression were analyzed by CVDK-8 analysis, a wound healing assay, and flow cytometry, respectively. Also, protein expression levels were quantified via Western blotting. In vitro and in silico findings were further validated by analyzing tumor and adjacent normal tissues from 65 luminal BC patients. Results: Curcumin inhibited the proliferation and migration of MCF-7 and T47D cells in a dose-dependent manner. Knockdown of hsa_circ_0001946 or overexpression of miR-7-5p significantly suppressed proliferation and migration and enhanced apoptosis in BC cells compared to the negative controls. Curcumin treatment led to the knockdown of hsa_circ_0001946, the overexpression of miR-7-5p, and the downregulation of hsa_circ_0001946, CKS2, TOP2A, and PARP1, while it upregulating miR-7-5p. The Western blot confirmed reduced CKS2 protein levels after curcumin treatment. The expression of both hsa_circ_0001946 and CKS2 was significantly upregulated in tumor tissues compared to that of matched adjacent normal tissues, whereas that of miR-7-5p was markedly downregulated. Conclusions: This preliminary study shows that curcumin suppresses BC tumorigenesis by modulating the hsa_circ_0001946/miR-7-5p/target gene axis. While these findings suggest a novel regulatory pathway and potential therapeutic targets, further in vivo validation and clinical trials are required to determine the translational relevance of curcumin in BC therapy.