How RNA Mods Shape Cancer Biology: Epitranscriptome-Mediated Regulation in High-Risk Neuroblastoma

Описание: How RNA Modifications Shape Cancer Biology: Epitranscriptome-Mediated Regulation in High-Risk Neuroblastoma

Epitranscriptomic regulation, particularly via N6-methyladenosine (m6A), plays a pivotal role in RNA metabolism and gene expression control. Although m6A dysregulation has been linked to several cancers, its contribution to neuroblastoma (NB), especially high-risk subtypes, remains poorly defined. High-risk NB, frequently driven by MYCN amplification and/or the alternative lengthening of telomeres (ALT) phenotype, remains a clinical challenge due to its resistance to conventional therapies.

To explore m6A’s functional role in NB pathogenesis, Tanmoy Mondal’s research group at the University of Gothenburg established a novel MYCN-driven neuroblastoma model by differentiating embryonic stem cells into trunk neural crest cells (tNCCs) and subsequently into sympathetic neurons. MYCN overexpression in this system faithfully recapitulates the undifferentiated state observed in NB tumors. Leveraging this model, the group discovered that MYCN and m6A act in concert to regulate the tNCC-to-sympathoadrenergic progenitor (SAP) cell transition.

In this webinar, Mondal will discuss the findings and how the team is applying a highly sensitive multi-modification profiling method optimized for low-input RNA in scarce clinical NB samples. The lab is actively refining and implementing such approaches to advance the detection of epitranscriptomic marks in challenging sample types and working to uncover how RNA modifications shape cancer biology, with the ultimate goal of translating epitranscriptomic insights into novel prognostic markers and therapeutic strategies for high-risk NB.

RNA modifications are a dynamic layer of gene regulation that control how and when genetic information is expressed. Unlike relatively stable and heritable DNA modifications, RNA modifications central to epitranscriptomics are reversible and enable rapid cellular responses to developmental and environmental cues. Advances in sequencing technologies have only recently made these modifications detectable, as they are largely invisible to standard NGS. Of the approximately 170 known RNA modifications, about 50 are found in humans, and only a small subset is commonly studied in mRNA and lncRNA, including m6A, inosine, pseudouridine, and m7G.

AlidaBio has developed the EpiPlex™ platform to make reading and quantifying changes in RNA modifications accessible to anyone doing RNA-Seq. Their antibody-free EpiPlex technology is available as both a kit and as a turnkey service. EpiPlex™ Duo-Mod service simultaneously maps and quantifies m6A and inosine RNA modifications alongside RNA expression in a single integrated report. The service is designed for researchers who need sensitive RNA modification detection, relative quantitation, and high-quality RNA-seq data from precious clinical samples including fresh frozen and FFPE tissues. EpiPlex™ Tri-Mod service, which adds pseudouridine profiling alongside m6A and inosine has been announced. The platform enables high-accuracy detection from as little as 20 ng of mRNA, and is paired with the companion EpiScout bioinformatics pipeline for high quality detection and relative quantitation. With a streamlined one-day workflow and sequencing requirements as low as 25 million reads, the EpiPlex platform makes RNA modification studies broadly accessible to researchers. Learn more at www.alidabio.com