2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
April 1st, 2025
Version: 1
Fondazione Istituto Italiano di Tecnologia
cancer biology
biorxiv

Synergic microRNAs suppress human glioblastoma progression by modulating clinically relevant targets

Rancati, S.Open in Google Scholar•Pereira, R. C.Open in Google Scholar•Schlich, M.Open in Google Scholar•Sgroi, S.Open in Google Scholar•Beatini, S.Open in Google Scholar•La Rosa, L.Open in Google Scholar•Giantomasi, L.Open in Google Scholar•Pelizzoli, R.Open in Google Scholar•Braccia, C.Open in Google Scholar•Spattini, C.Open in Google Scholaret al.

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.

Similar Papers

biorxiv
Wed Apr 02 2025
Attention Guided Mechanism Interpretable Drug-Gene Interaction (MIDI) Modeling for Cancer Drug Response Prediction and Target Effect Explanation
Cancer drug discovery using genetic information is still poorly developed. Precisely locating drug atoms and explaining the targeting effect is crucial in precision medicine since it helps understand the drug\'s mechanism of action. Much data has been collected regarding drug response against cancer cell lines, and many models predict the drug response based on genomic information. However, to our...
Wanyan, T.
•
Cai, L.
•
Nijhawan, D.
•
Posner, B.
...•
Xie, Y.
biorxiv
Wed Apr 02 2025
Lack of consistent effect of dietary fiber on immune checkpoint blockade efficacy across diverse murine tumor models
Immune checkpoint blockade (ICB) has transformed cancer treatment, but success rates remain low in most cancers. Recent research suggest that dietary fiber enhances ICB response in melanoma patients and murine preclinical models through microbiome-dependent mechanisms. Yet, the robustness of this effect across cancer types and dietary contexts remains unclear. Specifically, prior literature compar...
Roichman, A.
•
Reyes-Castellanos, G.
•
Chen, Z.
•
Chen, Z.
...•
Rabinowitz, J. D.
biorxiv
Wed Apr 02 2025
Epigenetic Modulation, Intra-tumoral Microbiome and Immunity in Early Onset Colorectal Cancer
Background: The incidence of colorectal cancer (CRC) in young adults (age of diagnosis < 50 years old) has been rapidly increasing. Although ~20% of early-onset (EO) CRC cases are due to germline mutations, the etiology of the majority of EOCRC cases remains poorly understood. Non-genetic factors such as environmental exposure and lifestyle changes are likely to have a direct link to the increased...
Jin, N.
•
Hoyd, R.
•
Yilmaz, A. S.
•
Zhu, J.
...•
Spakowicz, D.
biorxiv
Wed Apr 02 2025
Cell and nuclear size are associated with chromosomal instability and tumorigenicity in cancer cells that undergo whole genome doubling
Whole genome doubling (WGD) is a frequent event in cancer evolution associated with chromosomal instability, metastasis, and poor prognosis. While the genomic consequences of WGD are well documented, the effects of non-genetic alterations that accompany WGD, such as changes to cell and nuclear size, on tetraploid (4N) cancer cell physiology are less understood. Here, we show that cell and nuclear ...
Bloomfield, M.
•
Huth, S.
•
McCausland, D.
•
Saad, R.
...•
Cimini, D.
biorxiv
Wed Apr 02 2025
Selective targeting of oncogenic KRAS G12D using peptide nucleic acid oligomers attached to cell-penetrating peptides
KRAS is a proto-oncogene that contains activating mutations in up to 30% of tumors. Many conventional therapies inhibit both cancerous and normal cells, which may cause toxicity. Thus, programmable mutant-selective targeted inhibitors are needed. Peptide nucleic acids (PNAs) incorporate base sequences analogous to DNA, with modified peptide backbones instead of ribose-phosphate backbones, allowing...
Mondal, J.
•
Lam, D.
•
Gerritsen, M. E.
•
Brotz, T. M.
...•
Wolfe, A. L.
biorxiv
Wed Apr 02 2025
Futile wound healing drives mesenchymal-like cell phenotypes in human glioblastoma
Glioblastoma is the deadliest brain cancer, characterized by large cellular diversity whose complexity and organizing principles are only starting to be uncovered. Both neurodevelopment-like and mesenchymal-like cell states have been described in glioblastoma, with the latter being strongly implicated in malignancy and disease progression. However, the nature of these mesenchymal-like cell states ...
Mossi Albiach, A.
•
Janusauskas, J.
•
Kjaer Jacobsen, J.
•
Kapustova, I.
...•
Linnarsson, S.
biorxiv
Wed Apr 02 2025
Loss-of-Function genetic Screen Unveils Synergistic Efficacy of PARG Inhibition with Combined 5-Fluorouracil and Irinotecan Treatment in Colorectal Cancer
Colorectal cancer (CRC) remains a major global health concern, partly due to resistance to therapy and the lack of new effective treatments for advanced disease. The combination of 5-Fluorouracil (5FU, a thymidylate synthase inhibitor) and irinotecan (a topoisomerase 1 inhibitor) is widely used in first-line and subsequent treatments. This study aims to identify novel therapeutic targets to enhanc...
Queralt, C.
•
Moreta-Moraleda, C.
•
Costa, M.
•
Grau-Leal, F.
...•
Martinez-Balibrea, E.
biorxiv
Wed Apr 02 2025
Substrate stiffness regulates triple-negative breast cancer signaling through CXCR4 receptor dynamics
Biophysical properties of the extracellular matrix (ECM), such as mechanical stiffness, directly regulate behaviors of cancer cells linked to cancer initiation and progression. Cells sense and respond to ECM stiffness in the context of dynamic changes in biochemical inputs, such as growth factors and chemokines. While commonly studied as isolated inputs, mechanisms by which combined effects of mec...
Ho, K. K. Y.
•
Buschhaus, J. M.
•
Zhang, A.
•
Cutter, A. C.
...•
Luker, G. D.
biorxiv
Tue Apr 01 2025
FMO4 drives lung adenocarcinoma by stabilizing the MAT2A/MAT2B complex and hindering ferroptosis
Lung cancer is the leading cause of death by cancer in the world and finding new targets is a major medical need to tackle this disease. Here, upon proteomic analysis to identify common players in oncogenic EGFR- and KRAS-driven lung adenocarcinoma mouse models, we uncovered a largely unknown protein in cancer, flavin-containing monooxygenase 4 (FMO4), whose expression was increased in lung tumors...
Bracquemond, D.
•
Mahdizadeh, S. J.
•
Brunet, L.
•
Thomas, Q. D.
...•
Maraver, A.