首页|Center for Genomic Regulation Reports Findings in Leukemia (Integration of trans cription regulation and functional genomic data reveals lncRNA SNHG6's role in h ematopoietic differentiation and leukemia)
Center for Genomic Regulation Reports Findings in Leukemia (Integration of trans cription regulation and functional genomic data reveals lncRNA SNHG6's role in h ematopoietic differentiation and leukemia)
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By a News Reporter-Staff News Editor at Robotics & Machine Learning Daily News Daily News-New research on Oncology - Leukemia is the subject of a report. According to news reporting out of Catalonia, Spain, b y NewsRx editors, research stated, "Long non-coding RNAs (lncRNAs) are pivotal p layers in cellular processes, and their unique cell-type specific expression pat terns render them attractive biomarkers and therapeutic targets. Yet, the functi onal roles of most lncRNAs remain enigmatic." Financial supporters for this research include Israel Science Foundation, Israel Cancer Association. Our news journalists obtained a quote from the research from Center for Genomic Regulation, "To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with oth er genetic features to generate a machine learning model, which we have called I NFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Res ources). INFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) s creens across seven cell lines, and the algorithm was based on 71 genetic featur es. To validate the predictions, we selected candidate lncRNAs in the human K562 leukemia cell line and determined the impact of their knockdown (KD) on cell pr oliferation and chemotherapeutic drug response. We further performed transcripto mic analysis for candidate genes. Based on these findings, we assessed the lncRN A small nucleolar RNA host gene 6 (SNHG6) for its role in myeloid differentiatio n. Finally, we established a mouse K562 leukemia xenograft model to determine wh ether SNHG6 KD attenuates tumor growth in vivo. The INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nea rly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. In this respect, our cell-based and transcriptomic ana lyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation, SNHG6 transcription is regu lated by hematopoiesisassociated transcription factors. SNHG6 KD reduced the pr oliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte dif ferentiation. Using a xenograft mouse model, we demonstrate that SNHG6 KD attenu ated tumor growth in vivo. Our approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell typ e-specific manner, but also identified new lncRNAs with roles in hematopoiesis a nd leukemia."
CataloniaSpainEuropeCancerCyborg sDrugs and TherapiesEmerging TechnologiesGeneticsHealth and MedicineHe matologyHematopoiesisHematopoieticLeukemiaMachine LearningOncology
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