lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation

Delás, M. Joaquina; Jackson, Benjamin T.; Kovačević, Tatjana; Vangelisti, Silvia; Maravilla, Ester Munera; Wild, Sophia A; Stork, Eva Maria; Erard, Nicolas; Knott, Simon; Hannon, Gregory J.

doi:10.1016/j.celrep.2019.03.080

Cited by 31 publications

(23 citation statements)

References 44 publications

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“…A summary-data-based Mendelian randomization analysis that uses rs3809674 as an instrumental variable, predicts an effect of CEROX1 gene expression on glioma risk (Melin et al, 2017). Finally, it has recently been demonstrated in a mouse model of haematopoietic lineage differentiation that Cerox1 depletion may impair the contributions of stem cell or B cell differentiation to haematopoiesis (Delás et al, 2019).…”

Section: Resultsmentioning

confidence: 99%

The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity

Sirey

Roberts

Haerty

et al. 2019

eLife

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To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that Cerox1, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of Cerox1 cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone. Cerox1 function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation and, with miR-488-3p, represent novel targets for the modulation of complex I activity.

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Section: Resultsmentioning

confidence: 99%

The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity

Sirey

Roberts

Haerty

et al. 2019

eLife

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“…Long non-coding RNAs (lncRNAs) are a type of RNA of >200 nucleotides in length that do not encode for proteins. Following their discovery, lncRNAs were considered as ‘noises’ in the genome transcription process ( 19 , 20 ). However, subsequent studies demonstrated that lncRNAs regulate genes at a number of levels, including epigenetic, genomic transcription and post-transcriptional levels.…”

Section: Introductionmentioning

confidence: 99%

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

Xie

Zhang

et al. 2020

Oncol Lett

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Neuroblastoma (NB) is the most common type of extracranial solid tumor found in children. Despite several treatment options, patients with advanced stage disease have a poor prognosis. Previous studies have reported that enhancer of zeste homolog 2 (EZH2) and long non-coding RNAs (lncRNAs) have abnormal expression levels in NB and participate in tumorigenesis and NB development. However, the association between EZH2 and lncRNAs remain unclear. In the present study, RNA immunoprecipitation-sequencing (RIP-seq) was used to analyze the lncRNAs binding to EZH2. Following EZH2 knockdown via short hairpin RNA, RNA-seq was performed in shEZH2 and control groups in SH-SY5Y cells. Chromatin IP (ChIP)-seq was used to determine the genes that may be regulated by EZH2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the signaling pathways involved in NB. The results from RIP-seq identified 94 lncRNAs, including SNHG7, SNHG22, KTN-AS1 and Linc00843. Furthermore, results from RNA-seq demonstrated that, following EZH2 knockdown, 448 genes were up-and 571 genes were downregulated, with 32 lncRNAs up-and 35 downregulated and differentially expressed compared with control groups. Certain lncRNAs, including MALAT1, H19, Linc01021 and SNHG5, were differentially expressed in EZH2-knockdown group compared with the control group. ChIP-seq identified EZH2 located in the promoter region of 138 lncRNAs including CASC16, CASC15, LINC00694 and TBX5-AS1. In summary, the present study demonstrated that certain lncRNAs directly bound EZH2 and regulated EZH2 expression levels. A number of these lncRNAs that are associated with EZH2 may participate in NB tumorigenesis.

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“…It was demonstrated that lncRNAs were involved in various cellular functions, including cell proliferation, cell growth, cell differentiation and apoptosis. [8][9][10] The abnormal expression of lncRNAs was revealed in many diseases, including cancer, pulmonary fibrosis, and COPD. [11][12][13][14][15] Recently, increasing evidence has shown that HOXA cluster antisense RNA 2 (HOXA-AS2), a lncRNA located between and antisense to the human HOXA3 and HOXA4 genes, is associated with cell survival, proliferation and invasion.…”

Section: Introductionmentioning

confidence: 99%

<p>Microarray Analysis of Long Non-Coding RNAs in Lung Tissues of Patients with COPD and HOXA-AS2 Promotes HPMECs Proliferation via Notch1</p>

Zhou

Zhao

Zhou

et al. 2020

COPD

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Background and Objectives: Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of many diseases, including cancer, pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). In this study, we intended to identify the differentially expressed lncRNAs and the role of HOXA cluster antisense RNA 2 (HOXA-AS2) in patients with COPD. Methods: We analyzed lncRNA profiles of three non-COPD and seven COPD patients' lungs via microarray and then validated the expression of the top differentially expressed lncRNAs by using real-time polymerase chain reaction (PCR). To identify the mechanism of HOXA-AS2 during COPD pathogenesis and endothelial cell proliferation, we knocked down and overexpressed HOXA-AS2 with siRNA and lentivirus transfection approach in human pulmonary microvascular endothelial cells (HPMECs). Results: Among 29,150 distinct lncRNA transcripts, 353 lncRNAs were significantly (≥2-fold change and P<0.05) upregulated and 552 were downregulated in COPD patients. The fold change of HOXA-AS2 is 9.32; real-time PCR confirmed that HOXA-AS2 was downregulated in COPD patients. In in vitro experiments, cigarette smoke extract (CSE) treatment reduced the expression of HOXA-AS2 and cell proliferation of HPMECs. Knocking down HOXA-AS2 inhibited HPMECs proliferation and the expression of Notch1 in HPMECs. Overexpressing Notch1 could partly rescue the inhibition of cell viability induced by the silence of HOXA-AS2. Conclusion: Our results demonstrated that differentially expressed lncRNAs may act as potential molecular biomarkers for the diagnosis of COPD, and HOXA-AS2 was involved in the pathogenesis of COPD by regulating HPMECs proliferation via Notch1, which may provide a new approach for COPD treatment.

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lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation

Cited by 31 publications

References 44 publications

The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity

The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

<p>Microarray Analysis of Long Non-Coding RNAs in Lung Tissues of Patients with COPD and HOXA-AS2 Promotes HPMECs Proliferation via Notch1</p>

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