Title : Understanding the role of super enhancer MYCNOS-SE in chemoresistance of small cell lung cancer
Abstract:
Understanding the Role of Super-enhancer MYCNOS-SE in Chemoresistance of Small Cell Lung Cancer.
Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid progression and a high propensity for chemotherapy resistance. This presentation will discuss our recent findings on the super-enhancer MYCNOS-SE and its pivotal role in promoting chemoresistance in SCLC.
Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive the expression of key oncogenes and are crucial in establishing cell identity. In our study, we utilized RNA sequencing to identify highly expressed molecules associated with chemoresistance in SCLC. Through H3K27Ac and ATAC-Seq analyses, we identified MYCNOS-SE as a significant super-enhancer that regulates the expression of its target gene, MYCNOS.
Our findings demonstrate that MYCNOS is upregulated in both in vitro and in vivo models of SCLC, contributing to the development of chemotherapy resistance. We further elucidated the mechanism by which MYCNOS-SE recruits transcription factors CTCF and KLF15, enhancing MYCNOS expression and promoting survival in the presence of chemotherapeutic agents. Importantly, we discovered that MYCNOS, an antisense RNA of MYCN, modulates chemotherapy sensitivity through the NOTCH signaling pathway.
This research highlights the critical role of SE-regulated genes as biomarkers for chemoresistance in SCLC and suggests that MYCNOS could serve as a predictive marker for identifying patients who may benefit from NOTCH inhibitors. By understanding the molecular mechanisms underlying chemoresistance, we aim to provide insights that could lead to the development of novel therapeutic strategies targeting these pathways.
The presentation will also discuss the implications of our findings for future research directions and clinical applications, emphasizing the need for innovative approaches to overcome chemoresistance in SCLC and improve patient outcomes.
