Dataset Information

Exposure to ozone impacted Th1/Th2 imbalance of CD⁴⁺ T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling.

ABSTRACT: This investigation attempted to elucidate whether lncRNA PVT1-led miRNA axes participated in aggravating ozone-triggered asthma progression. One hundred and sixty-eight BALB/c mice were evenly divided into saline+air group, ovalbumin+air group, saline+ozone group and ovalbumin+ozone group. Correlations were evaluated between PVT1 expression and airway smooth muscle function/inflammatory cytokine release among the mice models. Furthermore, pcDNA3.1-PVT1 and si-PVT1 were, respectively, transfected into CD⁴⁺T cells and airway smooth muscle cells (ASMCs), and activities of the cells were observed. Ultimately, a cohort of asthma patients was recruited to estimate the diagnostic performance of PVT1. It was demonstrated that mice of ovalbumin+ozone group were associated with higher PVT1 expression, thicker trachea/airway smooth muscle and smaller ratio of Th1/Th2-like cytokines than mice of ovalbumin+air group and saline+ozone group (P<0.05). Moreover, pcDNA3.1-PVT1 significantly brought down Th1/Th2 ratio in CD⁴⁺ T cells by depressing miR-15a-5p expression and activating PI3K-Akt-mTOR signaling (P<0.05). The PVT1 also facilitated ASMC proliferation by sponging miR-29c-3p and motivating PI3K-Akt-mTOR signaling (P<0.05). Additionally, PVT1 seemed promising in diagnosis of asthma, with favorable sensitivity (i.e. 0.844) and specificity (i.e. 0.978). Conclusively, lncRNA PVT1-miR-15a-5p/miR-29c-3p-PI3K-Akt-mTOR axis was implicated in ozone-induced asthma development by promoting ASMC proliferation and Th1/Th2 imbalance.

SUBMITTER: Wei Y

PROVIDER: S-EPMC7803560 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Exposure to ozone impacted Th1/Th2 imbalance of CD<sup>4+</sup> T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling.

Wei Yangyang Y Han Baofen B Dai Wenjuan W Guo Shufang S Zhang Caiping C Zhao Lixuan L Gao Yan Y Jiang Yi Y Kong Xiaomei X

Aging 20201120 24

This investigation attempted to elucidate whether lncRNA PVT1-led miRNA axes participated in aggravating ozone-triggered asthma progression. One hundred and sixty-eight BALB/c mice were evenly divided into saline+air group, ovalbumin+air group, saline+ozone group and ovalbumin+ozone group. Correlations were evaluated between PVT1 expression and airway smooth muscle function/inflammatory cytokine release among the mice models. Furthermore, pcDNA3.1-PVT1 and si-PVT1 were, respectively, transfected ...[more]

PMID: 33223504

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Project description:Neuroblastoma (NB) is an enigmatic and deadliest pediatric cancer to treat. The major obstacles to the effective immunotherapy treatments in NB are defective immune cells and the immune evasion tactics deployed by the tumor cells and the stromal microenvironment. Nervous system development during embryonic and pediatric stages is critically mediated by non-coding RNAs such as micro RNAs (miR). Hence, we explored the role of miRs in anti-tumor immune response via a range of data-driven workflows and in vitro & in vivo experiments. Using the TARGET, NB patient dataset (n=249), we applied the robust bioinformatic workflows incorporating differential expression, co-expression, survival, heatmaps, and box plots. We initially demonstrated the role of miR-15a-5p (miR-15a) and miR-15b-5p (miR-15b) as tumor suppressors, followed by their negative association with stromal cell percentages and a statistically significant negative regulation of T and natural killer (NK) cell signature genes, especially CD274 (PD-L1) in stromal-low patient subsets. The NB phase-specific expression of the miR-15a/miR-15b-PD-L1 axis was further corroborated using the PDX (n=24) dataset. We demonstrated miR-15a/miR-15b mediated degradation of PD-L1 mRNA through its interaction with the 3'-untranslated region and the RNA-induced silencing complex using sequence-specific luciferase activity and Ago2 RNA immunoprecipitation assays. In addition, we established miR-15a/miR-15b induced CD8+T and NK cell activation and cytotoxicity against NB in vitro. Moreover, injection of murine cells expressing miR-15a reduced tumor size, tumor vasculature and enhanced the activation and infiltration of CD8+T and NK cells into the tumors in vivo. We further established that blocking the surface PD-L1 using an anti-PD-L1 antibody rescued miR-15a/miR-15b induced CD8+T and NK cell-mediated anti-tumor responses. These findings demonstrate that miR-15a and miR-15b induce an anti-tumor immune response by targeting PD-L1 in NB.

Dataset Information

Exposure to ozone impacted Th1/Th2 imbalance of CD⁴⁺ T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling.

Publications

Exposure to ozone impacted Th1/Th2 imbalance of CD<sup>4+</sup> T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Exposure to ozone impacted Th1/Th2 imbalance of CD4+ T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling.

Publications

Exposure to ozone impacted Th1/Th2 imbalance of CD<sup>4+</sup> T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Exposure to ozone impacted Th1/Th2 imbalance of CD⁴⁺ T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling.