SGOL1-AS1 enhances cell survival in acute myeloid leukemia by maintaining pro-inflammatory signaling

Epigenetic dysregulation is a key feature of most acute myeloid leukemia (AML). Recently, it has become clear that long noncoding RNAs (lncRNAs) can play a key role in epigenetic regulation, and consequently also dysregulation. Currently, our understanding of the requirements and roles of lncRNAs in...

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Main Authors: Ewan Selkirk, Rahima Patel, Anna Hoyle, Michael Lie-a-Ling, Duncan Smith, Joe Swift, Georges Lacaud
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844022026500
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author Ewan Selkirk
Rahima Patel
Anna Hoyle
Michael Lie-a-Ling
Duncan Smith
Joe Swift
Georges Lacaud
author_facet Ewan Selkirk
Rahima Patel
Anna Hoyle
Michael Lie-a-Ling
Duncan Smith
Joe Swift
Georges Lacaud
author_sort Ewan Selkirk
collection DOAJ
description Epigenetic dysregulation is a key feature of most acute myeloid leukemia (AML). Recently, it has become clear that long noncoding RNAs (lncRNAs) can play a key role in epigenetic regulation, and consequently also dysregulation. Currently, our understanding of the requirements and roles of lncRNAs in AML is still limited. Here, using CRISPRi screening, we identified the lncRNA SGOL1-AS1 as an essential regulator of survival in THP-1 AML cells. We demonstrated that SGOL1-AS1 interacts with chromatin-modifying proteins involved in gene repression and that SGOL1-AS1 knockdown is associated with increased heterochromatin formation. We also observed that loss of SGOLl-AS1 results in increased apoptosis and the downregulation of pro-inflammatory genes. In AML patients, high expression of SGOL1-AS1 correlates with both pro-inflammatory gene expression and poor survival. Altogether, our data reveal that SGOL1-AS1 is an essential regulator of cell survival in AML cell lines and a possible regulator of pro-inflammatory signaling in AML patients.
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spelling doaj.art-200fb99b57a4430ab65fcfda11acbdb02022-12-22T04:16:26ZengElsevierHeliyon2405-84402022-11-01811e11362SGOL1-AS1 enhances cell survival in acute myeloid leukemia by maintaining pro-inflammatory signalingEwan Selkirk0Rahima Patel1Anna Hoyle2Michael Lie-a-Ling3Duncan Smith4Joe Swift5Georges Lacaud6Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UKStem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UKDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UKStem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UKBiological Mass Spectrometry Facility, Cancer Research UK Manchester Institute, University of Manchester, Manchester, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UKDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UKStem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK; Corresponding author.Epigenetic dysregulation is a key feature of most acute myeloid leukemia (AML). Recently, it has become clear that long noncoding RNAs (lncRNAs) can play a key role in epigenetic regulation, and consequently also dysregulation. Currently, our understanding of the requirements and roles of lncRNAs in AML is still limited. Here, using CRISPRi screening, we identified the lncRNA SGOL1-AS1 as an essential regulator of survival in THP-1 AML cells. We demonstrated that SGOL1-AS1 interacts with chromatin-modifying proteins involved in gene repression and that SGOL1-AS1 knockdown is associated with increased heterochromatin formation. We also observed that loss of SGOLl-AS1 results in increased apoptosis and the downregulation of pro-inflammatory genes. In AML patients, high expression of SGOL1-AS1 correlates with both pro-inflammatory gene expression and poor survival. Altogether, our data reveal that SGOL1-AS1 is an essential regulator of cell survival in AML cell lines and a possible regulator of pro-inflammatory signaling in AML patients.http://www.sciencedirect.com/science/article/pii/S2405844022026500Acute myeloid leukemia (AML)Long noncoding RNA (lncRNA)Inflammatory signalingEpigenetic
spellingShingle Ewan Selkirk
Rahima Patel
Anna Hoyle
Michael Lie-a-Ling
Duncan Smith
Joe Swift
Georges Lacaud
SGOL1-AS1 enhances cell survival in acute myeloid leukemia by maintaining pro-inflammatory signaling
Heliyon
Acute myeloid leukemia (AML)
Long noncoding RNA (lncRNA)
Inflammatory signaling
Epigenetic
title SGOL1-AS1 enhances cell survival in acute myeloid leukemia by maintaining pro-inflammatory signaling
title_full SGOL1-AS1 enhances cell survival in acute myeloid leukemia by maintaining pro-inflammatory signaling
title_fullStr SGOL1-AS1 enhances cell survival in acute myeloid leukemia by maintaining pro-inflammatory signaling
title_full_unstemmed SGOL1-AS1 enhances cell survival in acute myeloid leukemia by maintaining pro-inflammatory signaling
title_short SGOL1-AS1 enhances cell survival in acute myeloid leukemia by maintaining pro-inflammatory signaling
title_sort sgol1 as1 enhances cell survival in acute myeloid leukemia by maintaining pro inflammatory signaling
topic Acute myeloid leukemia (AML)
Long noncoding RNA (lncRNA)
Inflammatory signaling
Epigenetic
url http://www.sciencedirect.com/science/article/pii/S2405844022026500
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