Biology subjects

Dobrucki, L. W.

Publications and source records attributed to Dobrucki, L. W..

3 recordsLinked to original sources

bioRxiv2026

The Role of the Receptor for Advanced Glycation End-Products in Cancer: Evidence from a Systematic Review and Meta-Analysis

The Receptor for Advanced Glycation End-products (RAGE) has been implicated in driving cancer growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarize and analyze current clinical and preclinical data to provide insight into the relationship between RAGE and cancer, cancer grade, metastasis, patient survival, and cellular processes. A multi-database search was performed to identify original clinical and preclinical research studies examining RAGE expression in cancer. After screening and review, 53 clinical and 233 preclinical studies were included. Associations of RAGE with clinical cancer outcomes were estimated using odds ratio (OR) and associated 95% confidence intervals (CI). The meta-analysis found that RAGE expression was highly correlated with cancerous tissue when compared to controls; high-grade tumors; regional lymph node invasion; and was somewhat negatively associated with patient survival. In addition, meta-analysis estimates of preclinical studies found positive associations between RAGE expression/activation and cancer growth, metastatic potential, evasion of apoptosis, and activated NF-{kappa}B expression. This systematic review and meta-analysis is the first comprehensive study through which both preclinical and clinical research in all available cancer types are assessed for correlations with RAGE expression and activation, demonstrating that RAGE does indeed play a significant role in cancer progression and that further research is warranted.

cancer biology↗

bioRxiv2024

Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells.

Small extracellular vesicles (sEVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME). Here, we investigate the mechanisms by which sEVs derived from neutrophils treated with the cholesterol metabolite, 27-hydroxycholesterol (27HC), influence breast cancer progression. sEVs released from 27HC treated neutrophils enhance epithelial-mesenchymal transition (EMT) and stem-like properties in breast cancer cells, resulting in loss of adherence, increased migratory capacity and resistance to cytotoxic chemotherapy. Decreased microRNAs (miRs) within the sEVs resulted in activation of the WNT/{beta}-catenin signaling pathway in recipient cells and suggest that this may be a predominant pathway for stem-like phenotype and EMT. Our findings underscore a novel mechanism by which 27HC-modulated neutrophils contribute to breast cancer pathophysiology through EV-mediated intercellular communication, suggesting potential therapeutic targets in cancer treatment.

cancer biology↗

bioRxiv2019

Overexpression of a non-muscle RBFOX2 isoform triggers cardiac conduction defects in myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is a multisystemic genetic disorder caused by a CTG trinucleotide repeat expansion in the 3' untranslated region of DMPK gene. Heart dysfunctions occur in nearly 80% of DM1 patients and are the second leading cause of DM1-related deaths. Despite these figures, the mechanisms underlying cardiac-based DM1 phenotypes are unknown. Herein, we report that upregulation of a non-muscle splice isoform of RNA binding protein RBFOX2 in DM1 heart tissue--due to altered splicing factor and microRNA activities--induces cardiac conduction defects in DM1 individuals. Mice engineered to express the non-muscle RBFOX2 isoform in heart via tetracycline-inducible transgenesis, or CRISPR/Cas9-mediated genome editing, reproduced DM1-related cardiac-conduction delay and spontaneous episodes of arrhythmia. Further, by integrating RNA binding with cardiac transcriptome datasets from both DM1 patients and mice expressing the non-muscle RBFOX2 isoform, we identified RBFOX2-driven splicing defects in the voltage-gated sodium and potassium channels, which can alter their electrophysiological properties. Thus, our results uncover a trans-dominant role for an aberrantly expressed RBFOX2 isoform in DM1 cardiac pathogenesis.

genetics↗