TY - JOUR T1 - LncRNA-CASC7 enhances corticosteroid sensitivity via inhibiting the PI3K/AKT signaling pathway by targeting miR-21 in severe asthma JO - Pulmonology T2 - AU - Liu,Jian-Hua AU - Li,Chen AU - Zhang,Chang-Hong AU - Zhang,Zhi-Hua SN - 25310437 M3 - 10.1016/j.pulmoe.2019.07.001 DO - 10.1016/j.pulmoe.2019.07.001 UR - https://www.journalpulmonology.org/en-lncrna-casc7-enhances-corticosteroid-sensitivity-via-articulo-S253104371930128X AB - BackgroundAsthma, a common chronic inflammatory disease, is treated with corticosteroid in most cases, but corticosteroid resistance in severe asthma patients seriously impairs the therapeutic effects. LncRNA-CASC7 inhibits cell proliferation and enhances drug sensitivity, but the molecular mechanisms of corticosteroid resistance in severe asthma are still unknown. MethodsAirway smooth muscle cells (ASMCs) from healthy and severe asthmatic subjects were used in this study. The expression of CASC7 and miR-21 were modified by transfection with the pcDNA3.1-CASC7, miR-21 mimics and inhibitor. MTT assay was conducted to measure cell proliferation. ELISA assay was used to determine the secretion of CCL5, CCL11 and IL-6. The phosphorylation of glucocorticoid receptor (GR) and the PI3K/AKT signaling were assessed by western blotting assays. qRT-PCR was used to analyze the expression of CASC7, miR-21 and PTEN. Dual-luciferase reporter assay was used to assess the interaction among CASC7, miR-21 and PTEN. ResultsCompared with AMSCs from severe asthma patients, dexamethasone inhibited cytokines (CCL5, CCL11 and IL-6) and promoted the phosphorylation of GR more significantly in normal AMSCs. CASC7 expression was suppressed while miR-21 expression and AKT activity were promoted in ASMCs from severe asthma patients. CASC7 promoted PTEN expression via directly inhibiting miR-21 expression. Overexpression of CASC7 suppressed the PI3K/AKT signaling pathway and promoted the inhibition effects of dexamethasone on cell proliferation and cytokines secretion via targeting miR-21. ConclusionCASC7 increased corticosteroid sensitivity by inhibiting the PI3K/AKT signaling pathway via targeting miR-21, which provided a promising potential target for designing novel therapeutic strategy for severe asthma. ER -