Biology subjects

Burlacu, A.

Publications and source records attributed to Burlacu, A..

3 recordsLinked to original sources

bioRxiv2026

Whole transcriptome analysis reveals ELK3 as a key driver of metastasis through regulation of 3D migration and stemness in triple-negative breast cancer cells

Metastasis is the leading cause of mortality in breast cancer and remains largely untargeted therapeutically. Identifying molecular drivers of metastatic progression is essential for developing effective treatments. This study investigated the role of the transcription factor ELK3 in triple-negative breast cancer (TNBC) metastasis by defining the cellular and molecular processes it regulates. MDA231 cells with ELK3 overexpression (OE) or knockdown (KD) were generated by lentiviral transduction. Transcriptomic alterations induced by ELK3-KD were analyzed by microarray and validated by RT-qPCR. Ingenuity Pathway Analysis and Gene Set Enrichment Analysis identified ELK3-dependent metastasis-associated pathways, which were functionally validated using 3D microfluidic migration assays, mammosphere formation assays, and flow cytometry/ AlamarBlue proliferation assays. High ELK3 expression correlated with a mesenchymal phenotype in BC cell lines and lymph node invasion in patient tumors. ELK3-KD significantly altered 740 genes, many linked to migration and stemness. Functionally, ELK3 enhanced 3D confined migration, likely through regulation of EMT, cell adhesion and protrusion formation. ELK3 also promoted cancer stem cell traits, potentially via hypoxia-related and WNT/{beta}-catenin, JAK/STAT3, TGF-{beta}, Notch1, and NF-{kappa}B signaling pathways. Additionally, ELK3 induced cellular quiescence while suppressing proliferation under adherent conditions. Overall, ELK3 acts as a pro-metastatic regulator in TNBC by promoting migration and stemness.

cancer biology↗

bioRxiv2026

miR-10b Mitigates Cardiac Fibrosis Associated with Aging and Myocardial Infarction via Attenuation of Lpar2 Signaling in Cardiac Fibroblasts

A impairs post-infarction cardiac repair through dysregulated fibroblast activation and excessive extracellular matrix (ECM) deposition, yet the molecular mechanisms driving the age-associated defects remain poorly defined. Here, we show that miR-10b upregulation in cardiac fibroblasts acts as an endogenous cardioprotective response to myocardial infarction (MI), limiting adverse remodeling through suppression of Lpar2 (lysophosphatidic acid receptor 2). Using integrative analysis of mRNA and small RNA transcriptomes in cardiac fibroblasts from young and aged mice, we demonstrate that miR-10b is enriched in cardiac fibroblasts and further upregulated in experimental models of cardiac fibrosis, but not in hepatic fibrosis. Temporal profiling after MI revealed a biphasic regulation of miR-10b, with downregulation during the early inflammatory phase followed by upregulation during the reparative and maturation phases. Gain-of-function experiments in cardiac fibroblasts showed that miR-10b suppressed proliferation, migration, and pro-fibrotic gene expression, while promoting apoptosis under inflammatory conditions. Integrated target prediction and transcriptomic analyses identified Lpar2 as a direct miR-10b target, validated by luciferase reporter assay and confirmed at both mRNA and protein levels. miR-10b overexpression attenuated lysophosphatidic acid (LPA)-induced fibroblast proliferation and collagen I/III synthesis, supporting an anti-fibrotic role. In vivo inhibition of miR-10b in aged mice exacerbated post-infarction ventricular dilatation and wall thinning, accompanied by increased fibrotic remodeling markers, consistent with enhanced extracellular matrix remodeling, providing in vivo evidence for this regulatory axis. Collectively, these findings establish miR-10b as a protective regulator of post-infarction remodeling and in aging heart through suppression of Lpar2-mediated fibroblast activation highlighting its potential as a therapeutic target in age-associated cardiac fibrosis.

cell biology↗

bioRxiv2024

miR-210 locus deletion disrupts cellular homeostasis; an integrated genetic study

MiR-210 is widely recognized as the quintessential hypoxia-responsive miRNA and thought to fine-tune various facets of cellular homeostasis. We hereby present an integrative appraisal of phenotypic and molecular repercussions of disrupting the corresponding locus in human and mouse cells using multiple genetic strategies. Briefly, MIR210 deletion led to decreased cellular fitness and suboptimal responses to several stress types. Transcriptomic comparisons using different profiling platforms, performed independently by members of this collaboration, revealed consistent deregulation of neighboring genes, in locus-disrupted cells. Interestingly, the anticipated enrichment in miR-210 targets failed to materialize in unbiased analyses. Our results point to the biological significance of unrecognized regulatory elements that overlap miRNA genes and should serve as note of caution for studies based for genetic disruption of such loci.

molecular biology↗