Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis

Dolcino, Marzia; Tinazzi, Elisa; Puccetti, Antonio; Lunardi, Claudio

doi:10.3390/cells8080816

Cited by 18 publications

(14 citation statements)

References 63 publications

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“…Total RNA was isolated from PBMC using TRIzol Reagent (Invitrogen, Carlsbad, CA, USA), following the manufacturer's instructions. PCR was performed by following the methods of Dolcino et al [27].…”

Section: Real-time Rt-pcrmentioning

confidence: 99%

Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy

Dolcino

Tinazzi

Puccetti

et al. 2020

JCM

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Fibromyalgia is a chronic disorder characterized by widespread pain and by several non-pain symptoms. Autoimmunity, small fiber neuropathy and neuroinflammation have been suggested to be involved in the pathogenesis of the disease. We have investigated the gene expression profile in peripheral blood mononuclear cells obtained from ten patients and ten healthy subjects. Of the 545,500 transcripts analyzed, 1673 resulted modulated in fibromyalgic patients. The majority of these genes are involved in biological processes and pathways linked to the clinical manifestations of the disease. Moreover, genes involved in immunological pathways connected to interleukin-17 and to Type I interferon signatures were also modulated, suggesting that autoimmunity plays a role in the disease. We then aimed at identifying differentially expressed Long non-coding RNAs (LncRNAs) functionally connected to modulated genes both directly and via microRNA targeting. Only two LncRNAs of the 298 found modulated in patients, were able to target the most highly connected genes in the fibromyalgia interactome, suggesting their involvement in crucial gene regulation. Our gene expression data were confirmed by real time PCR, by autoantibody testing, detection of soluble mediators and Th-17 polarization in a validation cohort of 50 patients. Our results indicate that genetic and epigenetic mechanisms as well as autoimmunity play a pivotal role in the pathogenesis of fibromyalgia.

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Section: Real-time Rt-pcrmentioning

confidence: 99%

Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy

Dolcino

Tinazzi

Puccetti

et al. 2020

JCM

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“…All these research studies indicated that lncRNAs are involved in the occurrence and development of various cancers. Furthermore, Dolcino et al [ 13 ] analyzed the transcript profiles of rheumatoid arthritis (RA) patients and healthy donors and found that lncRNA RP11-4989.15 plays an important role in RA pathogenesis. Another study screened eight important lncRNAs interacting with 52 differentially expressed genes enriched in asthma-associated pathways, and these lncRNAs have the potential to serve as underlying biomarkers useful for the future development of therapeutic strategies [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

The Identification of Childhood Asthma Progression-Related lncRNAs and mRNAs Suitable as Biomarkers Using Weighted Gene Coexpression Network Analysis

Hao

Zan

2021

Genetics Research

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Background. Asthma is a common chronic respiratory disease in children, seriously affecting children’s health and growth. This bioinformatics study aimed to identify potential RNA candidates closely associated with childhood asthma development within current gene databases. Methods. GSE65204 and GSE19187 datasets were screened and downloaded from the NCBI GEO database. Differentially expressed long noncoding RNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) were identified using the Bioconductor limma package in R, and these DE-mRNAs were used to perform biological process (BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Thereafter, weighted gene coexpression network analysis (WGCNA) was utilized to screen the modules directly related to childhood asthma, and a coexpression network of DE-lncRNAs and DE-mRNAs was built. Finally, principal component analysis (PCA) was performed. Results. In total, 7 DE-lncRNAs and 1060 DE-mRNAs, as well as 7 DE-lncRNAs and 1027 DE-mRNAs, were identified in GSE65204 and GSE19187, respectively. After comparison, 336 overlapping genes had the same trend of expression, including 2 overlapped DE-lncRNAs and 334 overlapped DE-mRNAs. These overlapped DE-mRNAs were enriched in 28 BP and 12 KEGG pathways. Eleven modules were obtained in GSE65204, and it was found that the purple, black, and yellow modules were significantly positively correlated with asthma development. Subsequently, a coexpression network including 63 DE-mRNAs and 2 DE-lncRNAs was built, and five KEGG pathways, containing 8 genes, were found to be directly associated with childhood asthma. The PCA further verified these results. Conclusion. LncRNAs LINC01559 and SNHG8 and mRNAs VWF, LAMB3, LAMA4, CAV1, ALDH1A3, SMOX, GNG4, and PPARG were identified as biomarkers associated with the progression of childhood asthma.

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“…RNA), we think that the characteristics of an RNA whether it is translated into a protein or not, cannot influence its possible use as a biomarker, thus we assume that involving this protein-coding gene in the evaluations did not cause bias in our results. HNRNPU was found to be implicated in several processes, including regulation of the innate immunity, proliferation and several diseases like cancers and eosinophilic asthma [ 28 , 29 , 41 – 45 ]. Our bioinformatic analysis showed that HNRNPU was associated with several FGFR2 related pathways.…”

Section: Discussionmentioning

confidence: 99%

Investigation of circulating lncRNAs as potential biomarkers in chronic respiratory diseases

et al. 2020

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Background In the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding RNAs (lncRNAs) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases. Methods In the discovery cohort, the gene expression level of 84 lncRNAs were measured in the blood of 24 adult patients including healthy controls and patients with asthma and COPD. In the replication cohort the expression of 6 selected lncRNAs were measured in 163 subjects including healthy controls and adults with allergic rhinitis, asthma, COPD and children with asthma. It was evaluated whether these lncRNAs can be used as diagnostic biomarkers for any studied disease. With systems biology analysis the biological functions of the selected lncRNAs were predicted. Results In the discovery cohort, the mean expression of 27 lncRNAs showed nominally significant differences in at least one comparison. OIP5-AS1, HNRNPU, RP11-325K4.3, JPX, RP11-282O18.3, MZF1-AS1 were selected for measurement in the replication cohort. Three lncRNAs (HNRNPU, RP11-325K4.3, JPX) expressed significantly higher in healthy children than in adult controls. All the mean expression level of the 6 lncRNAs differed significantly between adult allergic rhinitis patients and controls. RP11-325K4.3, HNRNPU and OIP5-AS1 expressed higher in allergic asthma than in non-allergic asthma. COPD and asthma differed in the expression of RP11-325K4.3 from each other. In examining of the lncRNAs as biomarkers the weighted accuracy (WA) values were especially high in the comparison of healthy controls and patients with allergic rhinitis. OIP5-AS1 and JPX achieved 0.98 and 0.9 WA values, respectively, and the combination of the selected lncRNAs also resulted in a high performance (WA = 0.98). Altogether, OIP5-AS1 had the highest discriminative power in case of three out of six comparisons. Conclusion Differences were detected in the expression of circulating lncRNAs in chronic respiratory diseases. Some of these differences might be utilized as biomarkers and also suggest a possible role of these lncRNAs in the pathomechanism of these diseases. The lncRNAs and the associated pathways are potential therapeutic targets in these diseases, but naturally additional studies are needed for the confirmation of these results.

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Long Non-Coding RNAs Target Pathogenetically Relevant Genes and Pathways in Rheumatoid Arthritis

Cited by 18 publications

References 63 publications

Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy

Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy

The Identification of Childhood Asthma Progression-Related lncRNAs and mRNAs Suitable as Biomarkers Using Weighted Gene Coexpression Network Analysis

Investigation of circulating lncRNAs as potential biomarkers in chronic respiratory diseases

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