Dataset Information

LncRNA TUG1 as a ceRNA promotes PM exposure-induced airway hyper-reactivity.

ABSTRACT: With the increased appreciation for the significance of noncoding RNAs (ncRNAs), the present research aimed to determine the role of competing endogenous RNA (ceRNA) in the process of particulate matter (PM) exposure-induced pulmonary damage. Alterations in messenger RNA (RNA), microRNA and long non-coding RNA (lncRNA) profiles of human bronchial epithelial (HBE) cells treated with PM were analyzed by microarray assays. Next, we identified that lncRNA taurine upregulated gene 1 (TUG1) acted as a competing endogenous RNA for microRNA-222-3p (miR-222-3p) and subsequently attenuated the inhibitory effect of miR-222-3p on CUGBP elav-like family member 1 (CELF1). The binding potency among ceRNAs was verified by RNA immunoprecipitation (RIP) assay and dual-luciferase reporter assay. Knockdown of TUG1 attenuated HBE cell apoptosis and cell cycle arrest by downregulation of CELF1 and protein 53 (p53). Further, we confirmed that Tug1/mir-222-3p/CELF1/p53 network aggravated PM-induced airway hyper-reactivity (AHR) in mice. In summary, our novel findings revealed that TUG1 triggered dysfunction of pulmonary cells followed by PM exposure by serving as a sponge for miR-222-3p and thereby upregulating the expression of CELF1and p53.

SUBMITTER: Li B

PROVIDER: S-EPMC8432742 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

lncRNA TUG1 as a ceRNA promotes PM exposure-induced airway hyper-reactivity.

Li Bin B Huang Nannan N Wei Shengnan S Xv Jie J Meng Qingtao Q Aschner Michael M Li Xiaobo X Chen Rui R

Journal of hazardous materials 20210416

With the increased appreciation for the significance of noncoding RNAs (ncRNAs), the present research aimed to determine the role of competing endogenous RNA (ceRNA) in the process of particulate matter (PM) exposure-induced pulmonary damage. Alterations in messenger RNA (RNA), microRNA and long non-coding RNA (lncRNA) profiles of human bronchial epithelial (HBE) cells treated with PM were analyzed by microarray assays. Next, we identified that lncRNA taurine upregulated gene 1 (TUG1) acted as a ...[more]

PMID: 34492818

Similar Datasets

Project description:IntroductionCeramide is the central substrate of sphingolipid metabolism and plays a key role in cellular signal transduction pathways, regulating apoptosis, differentiation, and chemotaxis. Alterations in airway ceramide levels are observed in multiple pulmonary diseases and recent human genetic association studies have linked dysregulation of sphingolipid regulatory genes with asthma pathogenesis.MethodsUtilizing myriocin, a potent inhibitor of sphingolipid synthesis, we evaluated the immune regulatory role of de novo ceramide generation in vitro and in vivo. Intratracheal myriocin was administered alone or during house dust mite sensitization (HDM) of BALB/C mice and airway hyper-responsiveness (AHR) was evaluated by invasive plethysmography followed by bronchial lavage (BAL) cytology and cytokine quantification.ResultsMyriocin inhibits and HDM exposure activates de novo ceramide synthesis in bone marrow-derived dendritic cells. Mice receiving intratracheal myriocin developed a mild airway neutrophilic infiltrate without inducing a significant increase in AHR. CXCL1 was elevated in the BAL fluid of myriocin-treated mice while the neutrophilic chemotactic factors anaphylatoxin C5a, leukotriene B4, and IL-17 were unaffected. HDM treatment combined with myriocin led to a dramatic enhancement of AHR (63% increase over HDM alone, p < 0.001) and increased granulocyte pulmonary infiltrates versus HDM or myriocin alone. Elevated Th2 T cell counts and Th2 cytokines/chemokines (IL5, IL13, CCL17) were observed in mice treated with combined HDM/myriocin compared to HDM alone. Myriocin-treated pulmonary CD11c+ cells stimulated with HDM secreted significantly more CXCL1 than cells stimulated with HDM alone while HDM stimulated airway epithelial cells showed no change in CXCL1 secretion following myriocin treatment.ConclusionsIntratracheal myriocin, likely acting via ceramide synthesis inhibition, enhances allergen-induced airway inflammation, granulocyte and Th2 lymphocyte recruitment, and allergen-induced AHR. Sphingolipid pathways may represent novel targets for possible future anti-inflammatory asthma medications.

Dataset Information

LncRNA TUG1 as a ceRNA promotes PM exposure-induced airway hyper-reactivity.

Publications

lncRNA TUG1 as a ceRNA promotes PM exposure-induced airway hyper-reactivity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets