Researchers identify a super-enhancer-regulated RNA-binding protein cascade that drives the growth of pancreatic ductal adenocarcinoma, a deadly form of pancreatic cancer. The discovery offers a promising new avenue for targeted therapy, potentially sidestepping severe side effects associated with other treatments.
By Neha MathurSep 10 2023Reviewed by Benedette Cuffari, M.Sc. In a recent study published in the journal Nature Communications, researchers identified a novel therapeutic target for pancreatic ductal adenocarcinoma , a lethal malignancy responsible for over 90% of all pancreatic cancer cases.
Super enhancers are specific regions in the genome that regulate the transformation and proliferation of cancer cells at the transcriptional level. To date, SEs coordinating the sustained increase in translation in PDAC remain largely unexplored, which has limited the development of effective PDAC treatments.
Study findings Previous studies have implicated several genes juxtaposed to genomic locations of SEs in processes dysregulated in cancer, such as JUN proto-oncogene in cell proliferation. In the current study. the H3 lysine 27 acetylation signal, a common SE identifier, was lower in normal cells as compared to the pancreatic cancer cell lines assessed in this study, thus supporting the relevance of SE-regulated hnRNP F expression in PDAC.
Related StoriesThe hnRNPF SE deleted cells were less proliferative in two-dimensional cultures and established smaller colonies in the three-dimensional in vitro assay. Re-expression of hnRNPF in these SE-deleted cells partially rescued the proliferative defect, which suggests that hnRNP F is the dominant SE-driven gene responsible for PDAC cell proliferation.
The researchers of the current study identified a SE-mediated RBP-regulated network that contributed to PDAC growth by enhancing mRNA translation, particularly ribosome biogenesis.