snoRNAs Offer Novel Insight and Promising Perspectives for Lung Cancer Understanding and Management

Mourksi, Nour‐El‐Houda; Morin, Chloé; Fenouil, Tanguy; Diaz, Jean‐Jacques; Marcel, Virginie

doi:10.3390/cells9030541

Cited by 48 publications

(37 citation statements)

References 81 publications

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“…Although the role of snoRNA in the progression of PAH is unclear, 30 differentially expressed snoRNAs were identified in this work. The roles of snoRNAs in lung cancer have been widely investigated (Mourksi et al, 2020). SNORA7B (Cui et al, 2021) and SNORA78 (Zheng et al, 2015) function as promoters in the tumorigenesis of non-small cell lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases

Wang

Jiang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Pulmonary arterial hypertension (PAH) is a severe cardiovascular disorder with high mortality. Multiple clinical diseases can induce PAH, but the underlying molecular mechanisms shared in PAHs associated with different diseases remain unclear. The aim of this study is to explore the key candidate genes and pathways in PAH associated with congenital heart disease (CHD-PAH), PAH associated with connective tissue disease (CTD-PAH), and idiopathic PAH (IPAH). We performed differential expression analysis based on a public microarray dataset GSE113439 and identified 1,442 differentially expressed genes, of which 80.3% were upregulated. Subsequently, both pathway enrichment analysis and protein–protein interaction network analysis revealed that the “Cell cycle” and “DNA damage” processes were significantly enriched in PAH. The expression of seven upregulated candidate genes (EIF2AK2, TOPBP1, CDC5L, DHX15, and CUL1–3) and three downregulated candidate genes (DLL4, EGFL7, and ACE) were validated by qRT-PCR. Furthermore, cell cycle-related genes Cul1 and Cul2 were identified in pulmonary arterial endothelial cells (PAECs) in vitro. The result revealed an increased expression of Cul2 in PAECs after hypoxic treatment. Silencing Cul2 could inhibit overproliferation and migration of PAECs in hypoxia. Taken together, according to bioinformatic analyses, our work revealed that “Cell cycle” and “DNA damage” process-related genes and pathways were significantly dysregulated expressed in PAHs associated with three different diseases. This commonality in molecular discovery might broaden the genetic perspective and understanding of PAH. Besides, silencing Cul2 showed a protective effect in PAECs in hypoxia. The results may provide new treatment targets in multiple diseases induced by PAH.

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Section: Discussionmentioning

confidence: 99%

Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases

Wang

Jiang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…All genes of SNORD115 cluster, for example are exclusively expressed in brain (Rogelj, 2006;Chamberlain, 2013;Jorjani et al, 2016). Although it has been reiterated in recent publications, (Cavaillé, 2017;Deogharia and Majumder, 2018;Chung et al, 2020), there is evidence that malignant cells of lung cancer tissue in primary cultures and lung cancer cell lines express members of SNORD115 cluster, in addition to many other SNORDs and SNORAs (Liao et al, 2010;Gao et al, 2014;Mourksi et al, 2020). Engineered expression of members of SNORD115 in brain tissues other than brain parenchyma -choroid plexus, has also been reported (Raabe et al, 2019).…”

Section: Discussionmentioning

confidence: 97%

Small nucleolar RNAs in plasma and their discriminatory power as diagnostic biomarkers of Alzheimer’s disease

Fitz

Wang

et al. 2021

Preprint

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The clinical diagnosis of Alzheimer's disease, at its early stage, remains a difficult task. Advanced imaging technologies and laboratory assays to detect Aβ; peptides Aβ42 and Aβ40, total and phosphorylated tau in CSF provide a set of biomarkers of developing AD brain pathology and facilitate the diagnostic process. The search for biofluid biomarkers, other than in CSF, and the development of biomarker assays have accelerated significantly and now represent the fastest-growing field in AD research. The goal of this study was to determine the differential enrichment of noncoding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EV) of AD patients and Cognitively Normal controls (NC). Using RNA-seq, we profiled four significant classes of ncRNAs: miRNAs, snoRNAs, tRNAs, and piRNAs. We report a significant enrichment of SNORDs - a group of snoRNAs, in AD samples compared to NC. To verify the differential enrichment of two clusters of SNORDs - SNORD115 and SNORD116, localized on human chromosome 15q11-q13, we used plasma samples of an independent group of AD patients and NC. We applied ddPCR technique and identified SNORD115 and SNORD116 with a high discriminatory power to differentiate AD samples from NC. The results of our study present evidence that AD is associated with changes in the enrichment of SNORDs, transcribed from imprinted genomic loci, in plasma EV and provide a rationale to further explore the validity of those SNORDs as plasma biomarkers of AD.

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“…When looking specifically at region-overlap, the majority of those genes included snoRNAs/scaRNAs. These non-coding RNAs have gained substantial interest lately due to their clinical relevance in various pathologies including lung cancer, host antiviral responses and their regulatory role in RNA modifications, splicing and telomerase activity [ 40 ]. Moreover, it was reassuring that our overlapping age-associated DMRs between both fetal and adult lung tissue datasets were also enriched in DNA-binding transcription factor activity with common gene-sets, which may represent regions of regulatory potential as well as targets of epigenetic therapy.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation perturbations may link altered development and aging in the lung

Kachroo

Morrow

Vyhlidal

et al. 2021

Aging

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Fetal perturbations in DNA methylation during lung development may reveal insights into the enduring impacts on adult lung health and disease during aging that have not been explored altogether before. We studied the association between genome-wide DNA-methylation and post-conception age in fetal-lung (n=78, 42 exposed to in-utero-smoke (IUS)) tissue and chronological age in adult-lung tissue (n=160, 114 with Chronic Obstructive Pulmonary Disease) using multi-variate linear regression models with covariate adjustment and tested for effect modification by phenotypes. Overlapping age-associations were evaluated for functional and tissue-specific enrichment using the Genotype-Tissue-Expression (GTEx) project. We identified 244 age-associated differentially methylated positions and 878 regions overlapping between fetal and adult-lung tissues. Hyper-methylated CpGs (96%) were enriched in transcription factor activity (FDR adjusted P=2x10 -33 ) and implicated in developmental processes including embryonic organ morphogenesis, neurogenesis and growth delay. Hypo-methylated CpGs (2%) were enriched in oxido-reductase activity and VEGFA-VEGFR2 Signaling. Twenty-one age-by-sex and eleven age-by-pack-years interactions were statistically significant (FDR<0.05) in adult-lung tissue. DNA methylation in transcription factors during development in fetal lung recapitulates in adult-lung tissue with aging. These findings reveal molecular mechanisms and pathways that may link disrupted development in early-life and age-associated lung diseases.

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snoRNAs Offer Novel Insight and Promising Perspectives for Lung Cancer Understanding and Management

Cited by 48 publications

References 81 publications

Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases

Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases

Small nucleolar RNAs in plasma and their discriminatory power as diagnostic biomarkers of Alzheimer’s disease

DNA methylation perturbations may link altered development and aging in the lung

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