Targeting and Characterizing Long Non-coding RNAs in Group 3 Medulloblastoma

PI:

Pietro Laneve

Email:

pietro.laneve@cnr.it

Affiliation:

Institute of Molecular Biology and Pathology (IBPM)

ORCID:

0000-0002-8865-4038

My research group at IBPM has a track record in investigating the roles of RNA in neuronal biological models. Our specific focus lies in comprehending the biogenesis, regulation, and mechanisms of action of noncoding RNAs within various contexts, including neuronal cell fate determination, neuromuscular pathophysiology, and nervous system cancers.

A substantial portion of our research efforts is directed towards elucidating the molecular underpinnings of neuronal cancers, where noncoding RNAs can serve as biomarkers, oncogenes, or tumor suppressors.

Within the National Center framework, my group is embarking on a research line dedicated to characterizing the noncoding side of Medulloblastoma (MB), a pediatric cerebellar tumor of embryonic origin and a leading cause of disease-related deaths in children.

Among the MB subtypes identified in the past decade, Group 3 (G3) represents the most aggressive and enigmatic one. G3 MB is driven by the MYC oncogene, yet the biochemical pathways implicated in its development remain largely unknown. To shed light on the etiology of G3 MB, our primary focus is to investigate the interplay between noncoding transcripts and MB driver genes, particularly the previously identified MYC-dependent oncogenic long noncoding RNAs (lncRNAs, Rea et al., 2021). The objective is i) to unravel the mechanisms at play in G3 MB, and ii) pinpoint specific targets for effective intervention.

The initial objective will be tackled through transcriptomics, interactomics, and molecular/cellular assays, aimed at deciphering the gene networks and mechanisms associated with MB lncRNAs.

The latter objective will be pursued through a collaborative effort with Dr. Ceci’s Lab (IBPM), which is pioneering innovative Human ferritin-based nanotechnologies for delivering antisense oligonucleotides (ASOs) to cancer cells. Within this partnership, our group will concentrate on designing LNA-GapmeR ASOs capable of suppressing MB lncRNA expression in the nucleus and cytoplasm. We will evaluate the effects of ASOs at both the molecular and phenotypic levels to determine the most efficacious RNA-based therapeutic approach.

In summary, this research endeavor seeks to advance our understanding of the functional aspects of MB lncRNA biology, identify potential candidates for developing targeted therapies for G3 MB, and provide insights into the dynamic behavior of ferritin nanovectors.

Relevant Publications

  1. Laneve P et al. The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity. Oncotarget. (2017) 8:31003-15. doi: 10.18632/oncotarget.16049

  2. Laneve P et al. Long Noncoding RNAs: Emerging Players in Medulloblastoma. Front Pediatr. (2019) 7:67. doi: 10.3389/fped.2019.00067

  3. Laneve P and Caffarelli E. The Non-coding Side of Medulloblastoma. Front Cell Dev Biol. (2020) 8:275. doi: 10.3389/fcell.2020.00275

  4. Rea J et al. Identification and Functional Characterization of Novel MYC-Regulated Long Noncoding RNAs in Group 3 Medulloblastoma. Cancers (Basel). (2021) 13:3853. doi: 10.3390/cancers13153853

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