Biology subjects

Tuntevski, K.

Publications and source records attributed to Tuntevski, K..

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↗

bioRxiv2023

Intralimb locomotor coordination in rats walking on asymmetric pegway

Complex movements such as walking or reaching are generated by a sequence of muscle actions. How these coordinated actions subserve complex movements and their recovery after disruption remains unknown. The use of high throughput recording-stimulation systems with microelectrode access to structures along the neuraxis may complement the neurological models in rodents. To this purpose, we have trained rats to perform the precise foot placement locomotor task that allows us to assess skilled locomotor movements. Animals were pretrained on the peg walkway task, which was configured to impose either symmetric or asymmetric (with overstepping) locomotor stepping at preferred stride length. Selected forelimb muscles were implanted with intramuscular differential electrodes. After a week of recovery, we collected electromyography from the implanted muscles and ground reaction forces from the array of force sensors embedded into walkway pegs. The temporal relationship between muscle bursts was measured for each intralimb set of muscles (n=13) in symmetric and asymmetric stepping. The sequence corresponded to the progression of muscle actions responsible for limb lift, flexion and transport, overground clearance, and preparation for ground contact. The stereotyped spatiotemporal sequence of muscle activity was persistent and mirroring across the asymmetric tasks. These patterns are similar to those observed in cats during locomotion with and without obstacles and reaching movements. These findings support the hypothesis that the profiles of muscle activations are qualitatively similar across quadrupeds during precise locomotor tasks. New and NoteworthyWe characterize for the first time the spatiotemporal muscle activation in rat forelimb during precise asymmetric stepping on asymmetrically placed rungs. Similar to cats, the intralimb pattern of muscle activation in rats was stereotypical. The elements of this pattern were changing in a lateralized fashion based on the direction of the imposed asymmetry. The similarity of pattern to that of cats supports the idea of similarity of neural control across cat and rat species.

neuroscience↗