Biology subjects

Pereira, R. C.

Publications and source records attributed to Pereira, R. C..

3 recordsLinked to original sources

bioRxiv2025

A microRNA-based Therapy against Human Medulloblastoma Validated in a Xenotransplant Model using Wild-Type Mouse Embryos

Medulloblastoma (MB) is the most prevalent malignant pediatric brain tumor. Its poor prognosis is driven by therapy-resistant cancer stem-like cells (CSCs), which are challenging to study in traditional preclinical models. MicroRNAs (miRNAs) modulate tumor-related pathways by repressing oncogenic gene expression, a function lost in cancer. We assessed the therapeutic potential of miRNA restoration in human MB from distinct subgroups, validated in a xenotransplant model using wild-type (WT) mouse embryos. Multi-omics, imaging, and in silico analyses were employed to identify underlying mechanisms and therapeutic targets. Human MB cells formed tumors in embryonic mouse brains that mirrored key MB features, including vascularized CSC niches and metastases. Restoration of underexpressed miRNAs reduced tumor growth and invasiveness in vitro and in vivo. These miRNAs synergistically repressed gene networks related to cell adhesion and RNA metabolism, shared oncogenic pathways across MB subgroups. Our embryonic xenotransplant model provides a clinically relevant platform for evaluating next-generation gene therapies in pediatric brain cancer.

cancer biology↗

bioRxiv2025

Synergic microRNAs suppress human glioblastoma progression by modulating clinically relevant targets

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by therapy-resistant glioma stem-like cells (GSCs) and extensive infiltration into surrounding brain tissue. MicroRNAs (miRNAs) are post-transcriptional regulators of oncogenic pathways, but their tumor-suppressive function is frequently lost in GBM. This study explores a multimodal therapeutic approach by restoring a combination of miRNAs to exploit their synergistic effects against GBM. Using patient-derived GBM cells cultured under stem cell-permissive conditions, we demonstrate that miRNA restoration reduces tumor growth, limits invasiveness, stemness and enhances sensitivity to temozolomide. In vivo studies in an orthotopic xenograft mouse model of GBM confirm the therapeutic efficacy and low toxicity of the nanoformulated miRNAs, following local injection. Multi-omics and computational analyses on different GBM subtypes reveal that these miRNAs synergistically suppress tumor-promoting extracellular matrix interactions, particularly through the collagen pathway, and downregulate genes associated with GBM progression. The identified miRNA targets correlate with glioma grade and poor patient prognosis, further underscoring their therapeutic potential. These findings highlight the promise of combinatorial miRNA therapy as a novel strategy for GBM treatment and suggest new molecular targets for theragnostic development.

cancer biology↗

bioRxiv2021

Erythroid overproduction of erythroferrone causes iron overload and developmental abnormalities in mice

The hormone erythroferrone (ERFE) is produced by erythroid cells in response to hemorrhage, hypoxia or other erythropoietic stimuli, and suppresses the hepatic production of the iron-regulatory hormone hepcidin, thereby mobilizing iron for erythropoiesis. Suppression of hepcidin by ERFE is thought to be mediated by interference with paracrine BMP signaling that regulates hepcidin transcription in hepatocytes. In anemias with ineffective erythropoiesis, ERFE is pathologically overproduced but its contribution to the clinical manifestations of these anemias is not well understood. We generated three lines of transgenic mice with graded erythroid overexpression of ERFE and showed that they developed dose-dependent iron overload, impaired hepatic BMP signaling and relative hepcidin deficiency. These findings add to the evidence that ERFE is a mediator of iron overload in conditions where ERFE is overproduced, including anemias with ineffective erythropoiesis. At the highest levels of ERFE overexpression the mice manifested decreased perinatal survival, impaired growth, small hypofunctional kidneys, decreased gonadal fat depots and neurobehavioral abnormalities, all consistent with impaired organ-specific BMP signaling during development. Neutralizing excessive ERFE in congenital anemias with ineffective erythropoiesis may not only prevent iron overload but may have additional benefits for growth and development. Key PointsO_LIChronic erythroid overproduction of erythroferrone dose-dependently suppresses hepcidin, causing iron overload even in the absence of anemia C_LIO_LIHigh level overexpression of erythroferrone can cause delayed growth, impaired kidney function and other developmental abnormalities consistent with altered BMP signaling C_LI

physiology↗