Biology subjects

Filipek, K.

Publications and source records attributed to Filipek, K..

3 recordsLinked to original sources

bioRxiv2026

Landscape of 8q24.3-Encoded microRNAs and Their Prognostic Impact in Ovarian Cancer

Ovarian cancer is the most lethal gynecological malignancy, largely because of late diagnosis and marked genomic instability, with high-grade serous ovarian cancer (HGSOC) representing its most common and aggressive subtype. Amplification of chromosome 8q24.3 is a recurrent event in HGSOC, yet the regulation and clinical relevance of the non-coding RNA output from this locus remain poorly defined. Here, we performed an integrative analysis of 8q24.3-encoded miRNAs in ovarian cancer using copy-number, transcriptomic, isoform-resolved, and clinical data from TCGA and NCBI datasets. We identified pronounced heterogeneity in miRNA abundance and strand usage across this locus. Copy-number gain broadly associated with increased miRNA expression, although this effect was not uniform across all candidates. Intronic miRNAs showed variable coupling with their host genes, indicating that mature miRNA output is shaped by both genomic dosage and post-transcriptional regulation. Isoform-level analysis revealed marked strand asymmetry and regulatory complexity, but did not strengthen copy-number or histotype associations compared with total miRNA measurements. Clinically, higher expression of miR-937, miR-4664, and miR-6849 was associated with improved overall survival in HGSOC. Functional enrichment of validated targets highlighted pathways related to cellular stress responses, senescence, p53 signaling, endocytosis, and metabolic adaptation. Together, these findings define 8q24.3 as a heterogeneous non-coding regulatory hub in ovarian cancer and provide a basis for future mechanistic and biomarker studies.

bioinformatics↗

bioRxiv2025

miR-6850 Drives Phenotypic Changes and Signaling in High Grade Serous Ovarian Cancer

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression, and their dysregulation is closely linked to cancer development. Ovarian cancer (OC), particularly the high-grade serous ovarian carcinoma (HGSOC) subtype, is the most lethal gynecological malignancy, primarily due to late-stage diagnosis and limited treatment options. Among the miRNAs encoded at the often amplified 8q24.3 region, miR-6850 has emerged as a potential candidate target owing to its genomic positioning inside this hotspot and its unexpectedly low expression in HGSOC tissues and cell lines. In silico investigations indicated that, despite the gain in MIR6850 copy number, its mature products, miR-6850-5p and miR-6850-3p, were expressed at low levels; notably, MIR6850 gene amplification was associated with enhanced disease-specific survival. Functional studies revealed that ectopic production of both isoforms in SKOV-3 and NIH:OVCAR3 cells inhibited proliferation, compromised clonogenic capacity, and disturbed cell cycle progression. Moreover, miR-6850 altered cell phenotype by facilitating mesenchymal-to-epithelial transition (MET), as shown by the overexpression of E-cadherin and {beta}-catenin and the downregulation of Slug and Vimentin. It also regulated cell adhesion and migration while reducing global protein synthesis via the downregulation of the PI3K/Akt/mTOR pathway. Our results together identify miR-6850 as a tumor-suppressive miRNA in HGSOC, demonstrating its diverse anti-oncogenic actions and underscoring its potential as a prognostic biomarker and therapeutic target in ovarian cancer.

cancer biology↗

bioRxiv2025

Ribosomal protein L5 (RPL5/uL18) I60V mutation is associated to increased translation and modulates drug sensitivity in T-cell acute lymphoblastic leukemia cells

Somatic mutations in ribosomal proteins (RPs), including RPL5, have been reported in approximately 10% of pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL). In cancer, the incorporation of mutant RPs into ribosomes often disrupts canonical ribosome function, thereby contributing to disease development. In this study, we aimed to characterize the effects of the RPL5-I60V mutation in the context of T-ALL, focusing on its impact on translation and cellular responses to a panel of compounds in vitro. Using CRISPR-Cas9, we generated a homozygous knock-in mutant in Jurkat cells and investigated its effects on ribosome biogenesis. We observed both quantitative and qualitative alterations in the production of the large ribosomal subunit. Ribosomes containing the mutant RPL5 protein exhibited intrinsically increased protein synthesis activity, which correlated with enhanced cellular proliferation. We then evaluated the response of these mutant cells to a panel of compounds targeting protein synthesis at various levels--including an MNK1 inhibitor, metformin, silvestrol, homoharringtonine, anisomycin, resveratrol, and hygromycin B--as well as cytarabine, a chemotherapeutic agent commonly used in T-ALL treatment. Our results showed that the RPL5-I60V mutation confers increased sensitivity to most of these compounds, with the exception of hygromycin B. This study advances our understanding of how oncoribosomes contribute to cancer pathogenesis and highlights the therapeutic potential of directly or indirectly targeting altered ribosomes, offering insights for the development of personalized treatment strategies. HighlightsO_LIRPL5 mutations have been reported in T-ALL C_LIO_LIRibosomes containing the RPL5 I60V mutation exhibit increased translational activity C_LIO_LIIncreased proliferation is observed in cells harboring the RPL5-I60V mutation C_LIO_LIRPL5-I60V confers a specific drug sensitivity profile C_LI Statements and DeclarationsCompeting interests: The authors declare that they have no conflict of interest.

cancer biology↗