A diagnostic circulating miRNA signature as orchestrator of cell invasion via TKS4/TKS5/EFHD2 modulation in human gliomas.

Autor: Díaz Méndez AB; Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy., Sacconi A; Biostatistics and Bioinformatics Unit, Clinical Trial Center, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Tremante E; Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy., Lulli V; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy., Caprara V; Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Rosanò L; Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.; Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR), Rome, Italy., Goeman F; SAFU Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Carosi M; Pathology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Di Giuliani M; Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy., Vari G; Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.; PhD Program in Molecular Medicine, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Silvani A; Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Pollo B; Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Garufi C; Medical-Oncology Unit, San Camillo Forlanini Hospital, Rome, Italy., Ramponi S; Medical-Oncology Unit, San Camillo Forlanini Hospital, Rome, Italy., Simonetti G; Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Ciusani E; Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Mandoj C; Clinical Pathology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Scalera S; SAFU Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.; PhD Program in Cellular and Molecular Biology, Department of Biology, University of Rome 'Tor Vergata', Rome, Italy., Villani V; Neuro-Oncology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Po A; Department of Experimental Medicine, Sapienza University, Rome, Italy., Ferretti E; Department of Experimental Medicine, Sapienza University, Rome, Italy., Regazzo G; Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. giulia.regazzo@ifo.it., Rizzo MG; Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. maria.rizzo@ifo.it.
Jazyk: angličtina
Zdroj: Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2023 Mar 17; Vol. 42 (1), pp. 66. Date of Electronic Publication: 2023 Mar 17.
DOI: 10.1186/s13046-023-02639-8
Abstrakt: Background: Altered microRNA profiles have been observed not only in tumour tissues but also in biofluids, where they circulate in a stable form thus representing interesting biomarker candidates. This study aimed to identify a microRNA signature as a non-invasive biomarker and to investigate its impact on glioma biology.
Methods: MicroRNAs were selected using a global expression profile in preoperative serum samples from 37 glioma patients. Comparison between serum samples from age and gender-matched controls was performed by using the droplet digital PCR. The ROC curve and Kaplan-Meier survival analyses were used to evaluate the diagnostic/prognostic values. The functional role of the identified signature was assessed by gain/loss of function strategies in glioma cells.
Results: A three-microRNA signature (miR-1-3p/-26a-1-3p/-487b-3p) was differentially expressed in the serum of patients according to the isocitrate dehydrogenase (IDH) genes mutation status and correlated with both patient Overall and Progression Free Survival. The identified signature was also downregulated in the serum of patients compared to controls. Consistent with these results, the signature expression and release in the conditioned medium of glioma cells was lower in IDH-wild type cells compared to the mutated counterpart. Furthermore, in silico analysis of glioma datasets showed a consistent deregulation of the signature according to the IDH mutation status in glioma tumour tissues. Ectopic expression of the signature negatively affects several glioma functions. Notably, it impacts the glioma invasive phenotype by directly targeting the invadopodia-related proteins TKS4, TKS5 and EFHD2.
Conclusions: We identified a three microRNA signature as a promising complementary or even an independent non-invasive diagnostic/prognostic biomarker. The signature displays oncosuppressive functions in glioma cells and impacts on proteins crucial for migration and invasion, providing potential targets for therapeutic intervention.
(© 2023. The Author(s).)
Databáze: MEDLINE
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