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Nuclear factor kappa B (NF-κB) signaling plays a central role in inflammation, immunity, cell survival, and cancer progression. Its constitutive activation is frequently observed in breast cancer, contributing to tumor growth, treatment resistance, and metastasis. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and may modulate NF-κB signaling in a subtype-specific or -independent manner. The aim of the study was to identify miRNAs that may potentially regulate the activity of genes associated with NF-κB signaling across five molecular subtypes of breast cancer in Polish women. Tumor and matched normal tissue samples were collected from 405 patients with five breast cancer subtypes: luminal A (n = 130), HER2-negative luminal B (n = 100), HER2-positive luminal B (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (TNBC, n = 43). Expression profile of selected NF-κB-related genes were evaluated using mRNA microarrays and RT-qPCR. Protein levels were assessed by ELISA. Candidate regulatory miRNAs were identified via miRNA microarrays and validated using the miRDB database. A consistent upregulation of MAP3K7, TAB2, TNFAIP3, CSNK2A1, BCL2L1, XIAP, CXCL2, and PLAU was observed across all subtypes, suggesting activation of canonical NF-κB signaling. Downregulation of specific miRNAs, miR-1297 and miR-30a (targeting MAP3K7), miR-134 (TAB2), miR-125b (TNFAIP3), and miR-4329 (XIAP), may contribute to this deregulation. For CSNK2A1, BCL2L1, CXCL2, and PLAU, no regulatory miRNAs meeting our criteria were identified. Our study reveals a subtype-independent activation of the canonical NF-κB signaling pathway in breast cancer, underpinned by consistent upregulation of key components (at both the transcript and protein levels. Dysregulation of specific miRNAs likely contributes to this altered gene expression. These findings suggest the presence of a common NF-κB-driven oncogenic program across molecular subtypes, with potential implications for developing miRNA-based therapeutic strategies targeting inflammation, survival signaling, and treatment resistance in breast cancer.

Breast cancer (BC) comprises heterogeneous subtypes with distinct molecular drivers and clinical behaviors. Among the key signaling pathways implicated in BC progression is the mitogen-activated protein kinase (MAPK) cascade, which regulates cell proliferation, apoptosis, and stress responses. microRNAs (miRNAs), as post-transcriptional regulators, are increasingly recognized as modulators of MAPK-associated genes, yet their integrated role across BC subtypes remains incompletely understood. This study included 405 patients with histopathologically confirmed BC, stratified into luminal A (LumA), HER2-negative luminal B, HER2-positive luminal B, non-luminal HER2-positive, and triple-negative breast cancer (TNBC). Control tissues were obtained from matched surgical margins. We performed mRNA profiling (Affymetrix microarrays), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), protein quantification (enzyme-linked immunosorbent assay (ELISA), and miRNA expression analysis. Predicted miRNA-mRNA interactions were analyzed using the miRDB database. Functional protein-protein interactions were explored using the STRING database. MAP3K1, MAP2K4, and TP53 were significantly downregulated across all subtypes, while PPM1D, LMTK3, and TGFB1 were upregulated, especially in TNBC. These alterations were supported by concordant changes at the protein level. Dysregulated miRNAs-miR-21-3p, miR-23c, miR-27a-3p, miR-205-3p, and miR-300-exhibited in-verse expression patterns relative to their predicted target genes. STRING analysis identified TP53 as a central hub, linking MAPK signaling with stress and apoptotic pathways. This integrated transcriptomic and miRNA profiling study reveals subtype-specific dysregulation of MAPK-associated genes and their miRNA regulators in BC, with TNBC exhibiting the most profound alterations. These findings provide insight into potential targets for personalized therapeutic strategies.

Background/Objectives: The Notch signaling pathway regulates cell fate, proliferation, and differentiation, and its dysregulation has been implicated in various cancers, including breast cancer. MicroRNAs (miRNAs) are critical post-transcriptional regulators that can modulate Notch pathway components. The aim of this study was to identify miRNAs that may potentially regulate the expression of Notch pathway-related genes across five molecular subtypes of breast cancer in Polish women. Methods: Tumor and adjacent normal tissue samples were collected from 405 patients with five breast cancer subtypes: luminal A (n = 130), HER2-negative luminal B (n = 100), HER2-positive luminal B (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (n = 43). Gene expression was profiled using mRNA microarrays and validated with RT-qPCR and ELISA. Candidate regulatory miRNAs were identified by miRNA microarrays and confirmed using the miRDB database. Results: APH1A, CTBP1, DTX1, HEY1, HEY2, JAG2, NOTCH4, TLE2, and TLE4 were consistently dysregulated across all breast cancer subtypes. Overexpression of HEY1 and JAG2 may be driven by decreased levels of miR-145, miR-98, and miR-381. Conversely, downregulation of TLE4 may be associated with elevated expression of miR-196a and miR-155. No regulatory miRNAs meeting the selection criteria were identified for APH1A, CTBP1, DTX1, HEY2, NOTCH4, or TLE2. Conclusions: The consistent alterations suggest the presence of a shared Notch-driven oncogenic signature in breast cancer, potentially driving cell proliferation, stemness, and resistance to therapy. These findings enhance our understanding of Notch signaling in breast cancer and propose novel miRNA–Notch interactions as candidate targets for therapeutic intervention.

Background/Objectives: Breast cancer represents a diverse group of malignancies and continues to rank among the leading causes of cancer-related deaths in women. Altered Hippo pathway signaling has been increasingly recognized as a contributor to tumor growth, therapeutic resistance, and metastatic spread. This study aimed to identify miRNAs targeting Hippo pathway-related genes that are consistently dysregulated across all five breast cancer subtypes. Methods: The study cohort included patients representing five breast cancer subtypes: 130 luminal A, 96 HER2-positive luminal B, 100 HER2-negative luminal B, 36 non-luminal HER2-positive, and 43 triple-negative breast cancer (TNBC). Tumor samples were collected during surgery, along with adjacent healthy tissue that served as controls. Expression of Hippo-related genes was analyzed using mRNA microarrays and validated with reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein levels were assessed via enzyme-linked immunosorbent assay (ELISA), while miRNA expression profiling was performed with miRNA microarrays. Potential mRNA targets were predicted using the miRDB database. Results: We identified consistent downregulation of STK4, RASSF6, and FGF1, alongside overexpression of BIRC5 and SERPINE1. miRNA analysis revealed that STK4 is potentially regulated by miR-522-3p, SERPINE1 by miR-199b-5p and miR-30a-3p, whereas RASSF6, FGF1, and BIRC5 appeared to be predominantly regulated at the transcriptional level. These alterations reflect both the suppression of upstream Hippo activation and activation of downstream oncogenic effectors across all subtypes. Conclusions: Our findings reveal a conserved Hippo dysregulation program in breast cancer, highlighting subtype-independent Hippo-related genes and their miRNA regulators as potential universal biomarkers and therapeutic targets, complementing subtype-specific treatment strategies.

This study aimed to assess the expression profile of messenger RNA (mRNA) and microRNA (miRNA) related to the dopaminergic system in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B (n = 196, including HER2−, n = 100; HER2+, n = 96), HER2+ (n = 36), and TNBC (n = 43); they underwent surgery, during which tumor tissue was removed along with a margin of healthy tissue (control material). The molecular analysis included a microarray profile of mRNAs and miRNAs associated with the dopaminergic system, a real-time polymerase chain reaction preceded by reverse transcription for selected genes, and determinations of their concentration using enzyme-linked immunosorbent assay (ELISA). The conducted statistical analysis showed that five mRNAs statistically significantly differentiated breast cancer sections regardless of subtype compared to control samples; these were dopamine receptor 2 (DRD2), dopamine receptor 3 (DRD3), dopamine receptor 25 (DRD5), transforming growth factor beta 2 (TGF-β-2), and caveolin 2 (CAV2). The predicted analysis showed that hsa-miR-141-3p can regulate the expression of DRD2 and TGF-β-2, whereas hsa-miR-4441 is potentially engaged in the expression regulation of DRD3 and DRD5. In addition, the expression pattern of DRD5 mRNA can also be regulated by has-miR-16-5p. The overexpression of DRD2 and DRD3, with concomitant silencing of DRD5 expression, confirms the presence of dopaminergic abnormalities in breast cancer patients. Moreover, these abnormalities may be the result of miR-141-3P, miR-16-5p, and miR-4441 activity, regulating proliferation or metastasis.

The aim of this study was to identify miRNAs that could potentially influence the activity of SMAD proteins involved in TGFβ signal transduction in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B HER2− (n = 100), luminal B HER2+ (n = 96), non-luminal HER2+ (n = 36), and TNBC (n = 43). During surgery, tumor tissue was removed along with a margin of healthy tissue (control). Molecular analysis included determination of the expression of genes related to SMAD protein signal transduction using mRNA microarrays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression was determined using an enzyme-linked immunosorbent assay (ELISA). The miRNA profiling was performed using miRNA microarrays and the miRDB database. SMAD3 and SMAD5 were overexpressed in all types of breast cancer, which could be related to the reduced expression of miR-145, and the findings for SMAD4 and miR-155 were similar. Additionally, the level of SMAD7 was reduced, which may be due to the low activity of miR-15b and miR21b. This study determined the gene expression profiles involved in SMAD protein signal transduction across five different types of breast cancer and identified the miRNAs potentially regulating their activity. Overexpression of SMAD3, SMAD4, and SMAD5 suggests excessive activation of the TGFβ pathway, potentially promoting tumor growth and development. Concurrently, a significant reduction in SMAD7 expression removes inhibitory control in the TGFβ pathway, a phenomenon that is particularly evident in more aggressive breast cancer types.

Breast cancer is the most commonly diagnosed cancer in women. The Wnt pathway is involved in the regulation of cell proliferation, differentiation, survival, and migration. Its disruption may promote the induction of breast cancer and its further development. The aim of the study was to identify micro RNA (miRNAs) that could potentially influence the activity of Wnt-related genes in five types of breast cancer in Polish women. Study included patients with five breast cancer subtypes: 130 luminal A, 96 HER2-positive luminal B, 100 HER2-negative luminal B, 36 non-luminal HER2-positive, 43 triple negative breast cancer (TNBC). Tumor tissue was removed during surgery along with a margin of healthy tissue (control group). Expression profile of Wnt-related genes was assessed with mRNA microarrays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression was conducted with enzyme-linked immunosorbent assay (ELISA). miRNA profiling was carried out with miRNAs microarrays and the miRDB database. Reduced activity of miR-130a could be related to overexpression of CCND1 and GSK3B . Similarly for miR-199a and GSK3B . High activity of miR-2115 could be associated with downregulation of TCF7L2 . WNT5 A overexpression may be linked to low levels of miR-497. In addition, study revealed increased levels of APC , DVL3 , LEF1 with reduced activity of FZD4 and TCF7L1 in all five subtypes of breast cancer.

Background/Objectives: In this study, serum selenium levels in patients with Crohn’s disease (CD) and ulcerative colitis (UC) were evaluated to identify potential predictive markers of disease activity. Conducted in 100 inflammatory bowel disease (IBD) patients (54 CD, 46 UC) and 100 healthy controls, this research provides novel insights through focusing on the regional selenium status of people with IBD in the Polish population, a demographic with limited existing data. Methods: Selenium concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). Results: Significantly lower levels of selenium were observed in CD (64.79 µg/L ± 12.15 µg/L) and UC (68.61 µg/L ± 11.43 µg/L) patients when compared with the controls (90.52 ± 12.00 µg/L, p < 0.0001). Regression analysis identified leukocyte and erythrocyte counts and bilirubin as significant predictors of selenium levels in UC patients, while no significant predictors were found for CD. Conclusions: The findings suggest that selenium deficiency is linked to IBD and may serve as a non-invasive biomarker for disease severity, particularly in UC. This practical approach offers a potential alternative to invasive procedures such as endoscopy for monitoring disease progression. However, further research is needed to confirm these findings in larger populations and explore the therapeutic role of selenium supplementation in IBD management.