Down‐Regulation of miR‐19a as a Biomarker for Early Detection of Silicosis

Yang, Zhen; Li, Qian; Yao, Sanqiao; Zhang, Ge; Xue, Rong; Li, Guoliang; Wang, Yizheng; Wang, Shixin; Wu, Ruichang; Gao, Hongsheng

doi:10.1002/ar.23381

Cited by 17 publications

(18 citation statements)

References 30 publications

(31 reference statements)

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“…Meanwhile, Yang et al . reported that downregulation of miRNA‐19a acts as an early detection biomarker of SPF . Our results identifying miRNA‐4508 as a diagnostic biomarker of SPF will further enrich the field of SPF biomarker research.…”

Section: Discussionsupporting

confidence: 52%

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miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

Chu

Wang³

et al. 2019

Respirology

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Background and objective: This study aimed to identify miRNA as potential diagnostic biomarkers for silicarelated pulmonary fibrosis (SPF). Methods: We first performed a comprehensive miRNAseq screening in PBL of eight subjects exposed to silica dust (four individuals with SPF and four healthy controls). The promising miRNA were then evaluated in the first-stage validation using an independent GEO data set (GSE80555) of 6 subjects (3 individuals with SPF and 3 healthy controls), followed by a second-stage validation using 120 subjects exposed to silica dust (60 individuals with SPF and 60 healthy controls). Results: Thirty-five miRNA showed strong expression differences in miRNA-seq screening, while miRNA-4508 (P = 9.52 × 10 −3 ) was retained as a candidate after the first-stage validation (GSE80555), which was further confirmed in the second-stage validation with similar and strong effect (P = 9.93 × 10 −17 ). ROC analysis showed that miRNA-4508 could distinguish SPF cases from healthy controls with high AUC (0.886), with sensitivity of 81.7% and specificity of 86.7%. In addition, the miRNA-4508 upstream rs6576457 mutant A allele exhibited a strong association with susceptibility to SPF (OR = 1.64, 95% CI = 1.20-2.23, P = 0.002), while eQTL analysis revealed a potential association between different genotypes of rs6576457 and miRNA-4508 expression (P = 0.068) in 60 healthy subjects with silica dust exposure.Conclusion: miRNA-4508 may be a potential diagnostic marker for SPF, and rs6576457, a functional variant of miRNA-4508, may affect SPF susceptibility. The detailed mechanism of action of this miRNA remains to be elucidated. † Logistic regression analysis adjusted for age, gender, years of silica dust exposure and pack-years of smoking. miRNA, microRNA; OR, odds ratio; SNP, single nucleotide polymorphism.

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Section: Discussionsupporting

confidence: 52%

“…The miRNA expression data of the peripheral blood leucocytes from three SPF cases and controls were downloaded from the Gene Expression Omnibus (GEO) data set (GSE80555) (http://www.ncbi.nlm.nih.gov/geo/), which uses the Human microRNA OneArray v5 (Phalanx Biotech Group, Taiwan, China) as a platform to identify miRNA as SPF biomarkers …”

Section: Methodsmentioning

confidence: 99%

miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

Chu

Wang³

et al. 2019

Respirology

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“…The qPCR reaction conditions were 40 cycles of 95°C for 30 s, 95°C for 5 s, and 60°C for 30 s. The PCR results were verified by the melting curve. Relative expression was calculated by the cycle threshold (Ct) values and the 2 -△△Ct method using β-actin as an internal control [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-146a suppresses rheumatoid arthritis fibroblast-like synoviocytes proliferation and inflammatory responses by inhibiting the TLR4/NF-kB signaling

Liu

Zhang

et al. 2018

Oncotarget

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This study investigated whether microRNA-146a (miR-146a) mediating TLR4/NF-κB pathway affected proliferation and inflammatory responses of rheumatoid arthritis fibroblast-like synoviocytes from 12 RA patients (RA-FLSs). FLSs in the logarithmic growth phase were assigned into the control, miR-146a mimic miR-146a inhibitor, Tak-242 (treated with TLR4/NF-κB pathway inhibitor) and mimic + lipopolysaccharide (LPS) groups. Cell proliferation and apoptosis were detected using CCK-8 assay and flow cytometry. The expression of miR-146a, TLR4/NF-κB pathway-related proteins and cytokines were determined by RT-qPCR, western blotting and ELISA, and the release of NO by Greiss reaction. RA rat models were constructed and the primary cells were classified into the control, negative control (NC), miR-146a mimic, miR-146a inhibitor, Tak-242, mimic + LPS, and TLR4 groups. Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen (PCNA) and intercellular adhesion molecular-1 (ICAM-1). The results showed that miR-146a levels were lower in RA-FLSs than control fibroblasts. miR-146a mimic and Tak-242 decreased RA-FLS proliferation and increased RA-FLS apoptosis, while miR-146a inhibitor had an opposite trend. miR-146a mimic and Tak-242 also decreased expression of TLR4, NF-κB, IL-1β, IL-6, IL-8, IL-17, COX-2, MMP-3, Seprase, and iNOS, as well as reduced NO level in RA-FLSs while miR-146a inhibitor and TLR4 increased them. TLR4 and NF-κB levels and the positive rates of PCNA and ICAM-1 expressions were lower in RA-FLSs from RA rats given miR-146a mimic from control or miR-146a inhibitor-treated rats. These results suggest that miR-146a inhibits the proliferation and inflammatory response of RA-FLSs by down-regulating TLR4/NF-κB pathway.

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“…Detailed information concerning primer sequences is shown in Supplementary Table 8. Results were quantified using Ct values (delta-delta Ct) method [95].…”

Section: Rna Extraction and Qrt-pcrmentioning

confidence: 99%

Sigma-1 receptor is involved in diminished ovarian reserve possibly by influencing endoplasmic reticulum stress-mediated granulosa cells apoptosis

Jiang

Cui

Zhang

et al. 2020

Aging

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Sigma non-opioid intracellular receptor 1 (sigma-1 receptor), a non-opioid transmembrane protein, is located on cellular mitochondrial membranes and endoplasmic reticulum. Current research has demonstrated that sigma-1 receptor is related to human degenerative diseases. This study is focused on the effects of sigma-1 receptor on the pathophysiological process of diminished ovarian reserve (DOR) and granulosa cells (GCs) apoptosis. Sigma-1 receptor concentration in follicular fluid (FF) and serum were negatively correlated with basal follicle-stimulating hormone (FSH) and positively correlated with anti-mullerian hormone (AMH), antral follicle count (AFC). Sigma-1 receptor reduction in GCs was accompanied by endoplasmic reticulum stress (ERS)-mediated apoptosis in women with DOR. Plasmid transfection was used to establish SIGMAR1-overexpressed and SIGMAR1-knockdown human granulosa-like tumor (KGN) cell and thapsigargin (TG) was used to induce ERS KGN cells. We found that KGN cells treated with endogenous sigma-1 receptor ligand dehydroepiandrosterone (DHEA) and sigma-1 receptor agonist PRE-084 showed similar biological effects to SIGMAR1-overexpressed KGN cells and opposite effects to SIGMAR1knockdown KGN cells. DHEA may improve DOR patients' pregnancy outcomes by upregulating sigma-1 receptor and downregulating ERS-mediated apoptotic genes in GCs. Thus, sigma-1 receptor may be a potential ovarian reserve biomarker, and ligand-mediated sigma-1 receptor activation could be a future approach for DOR therapy.

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Down‐Regulation of miR‐19a as a Biomarker for Early Detection of Silicosis

Cited by 17 publications

References 30 publications

miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

MicroRNA-146a suppresses rheumatoid arthritis fibroblast-like synoviocytes proliferation and inflammatory responses by inhibiting the TLR4/NF-kB signaling

Sigma-1 receptor is involved in diminished ovarian reserve possibly by influencing endoplasmic reticulum stress-mediated granulosa cells apoptosis

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