Summary:. Cancer cells display extensive heterogeneity that influences therapy response and clinical outcome, yet the underlying mechanisms remain incompletely understood. Recent studies reveal that t...

Wnt/β-catenin signalling is dysregulated across several haematological malignancies, including acute myeloid leukaemia (AML), where is lacks effective targeting strategies. Previously, we discovered that β-catenin interacts with several RNA-binding proteins (RBP), and binds mRNA indirectly, indicating contributions to the post-transcriptional landscape of leukaemia cells. Here, we found the most frequent RBP-binding motif amongst β-catenin-bound mRNAs was the GGAG motif targeted by the oncofoetal expressed miRNA-regulating RBP LIN28B. We detected the β-catenin:LIN28B interaction in lymphoid and myeloid cell lines, and primary human CD34⁺ fetal liver-derived haematopoietic stem cells. LIN28B positively regulated Wnt signalling capacity by regulating LEF1 expression through a post-transcriptional mechanism requiring the let7 miRNA axis. Further miRNA sequencing of β-catenin- and LIN28B-depleted myeloid cells revealed both potential cooperative and antagonistic function in miRNA regulation. Finally, dual-targeting both β-catenin and LIN28B through either genetic or pharmacological means preferentially killed AML cells. These data reveal a potential novel synthetically lethal relationship in AML which could be exploited in the rare AML subsets where LIN28B expression becomes reactivated ### Competing Interest Statement The authors have declared no competing interest. Kay Kendall Leukaemia Fund, https://ror.org/03j2wfg84, KKL1051, KKL1446 Leukaemia & Myeloma Research UK, 4-5/06.21R Children’s Cancer & Leukaemia Group, CCLGA 2023 16 Morgan Republic of Türkiye Ministry of National Education

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Abstract. DNA methylation is a widely studied epigenetic mark and a powerful biomarker of cell type, age, environmental exposures, and disease. Whole-genom

Der Wissenschaftsrat (WR) fordert eine grundlegende Reform der Personalstrukturen im deutschen Wissenschaftssystem. Das Ziel sind attraktive, vielfältige Stellen mit klar strukturierten Entwicklungsoptionen, die die Wissenschaftseinrichtungen in der Konkurrenz um Fachkräfte sowie im internationalen Wettbewerb stärken. Nötig ist ein Personalgefüge, das den immer stärker ausdifferenzierten Anforderungen an die und aus der Wissenschaft gerecht wird und attraktive Dauerstellen ergänzend zur Professur bietet.

Nature Genetics - Latent embedding multivariate regression models multi-condition single-cell RNA-seq using a continuous latent space, enabling data integration, per-cell gene expression prediction...

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