Integrative omics has posed new challenges in modern precision medicine, particularly in oncology, including i) the identification of new tumor markers for early, precise, and non-invasive diagnostics, and ii) the discovery of innovative molecular targets for therapeutic applications. Our studies on medulloblastoma, a highly malignant childhood tumor, have contributed to identifying RNA molecules that meet these criteria. These are long non-coding RNAs, transcripts without the ability to produce proteins but crucial in regulating biological processes and involved in tumor initiation and progression. Through experimental analyses in tumor cell lines and assessments of their levels in primary tumors, we identified RNAs that are aberrantly expressed in medulloblastoma compared to healthy tissue. Further molecular characterizations have led us to conclude that these RNAs serve as new biomarkers for stratifying the various subgroups of medulloblastoma and as potential targets for targeted therapy.
The long non-coding RNAs we have identified in various medulloblastoma subgroups possess molecular characteristics that make them superior tumor biomarkers compared to "canonical" transcripts. The tumor-specific expression pattern enables early diagnosis not only of the tumor type but also of the tumor subgroup, facilitating targeted therapies. In general, the increase in their expression levels correlated with the severity of the tumor can provide prognostic information regarding the tumor stage. Their high stability in bodily fluids makes them excellent candidates for non-invasive screening compared to current biopsies. From a therapeutic perspective, based on their specificity and functional versatility, long non-coding RNAs can represent optimal and easily targetable therapeutic substrates, for example, through the development of RNA-based drugs. We have identified modified antisense oligonucleotides capable of recognizing and silencing, through base complementarity, overexpressed long non-coding RNAs in the pathology. Restoring their expression to physiological levels allows for the recovery of molecular cascade patterns deregulated by the transcript and for the mitigation of tumor characteristics in vitro.