Chronic obstructive pulmonary disease (COPD) is a common airway disease characterized by an exaggerated pulmonary inflammatory response. Long noncoding MIR155 host gene (lncRNA MIR155HG) has been identified to be related to the macrophage polarization in COPD. However, the detailed function of MIR155HG in cigarette smoke (CS)-mediated COPD remains largely unknown. The expression level of MIR155HG was elevated while miR-218-5p was decreased in lung tissues of smokers without or with COPD, especially in smokers with COPD, and cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cell (HPMECs) in a dose-and time-dependent manner. Then, functional experiments showed that MIR155HG deletion could reverse CSE exposure-induced apoptosis and inflammation in HPMECs. MiR-218-5p was confirmed to be a target of MIR155HG and rescue assay showed miR-218-5p inhibitor attenuated the inhibitory action of MIR155HG knockdown on CSE-induced HPMECs. Subsequently, miR-218-5p was found to target bromodomain containing 4 (BRD4) directly, and miR-218-5p overexpression overturned CSE-induced injury of HPMECs via regulating BRD4. Additionally, co-expression analysis indicated MIR155HG indirectly regulated BRD4 expression in HP-MECs via miR-218-5p. Thus, we concluded that MIR155HG contributed to the apoptosis and inflammation of HPMECs in smoke-related COPD by regulating miR-128-5p/BRD4 axis, providing a novel insight on the pathogenesis of COPD and a therapeutic strategy on COPD treatments.According to the prediction of DIANA-LncBaseV2 prediction program, miR-218-5p might be a potential target of MIR155HG ( Figure 3A). To verify this prediction, luciferase reporter assay was performed and we found miR-218-5p mimic transfection reduced the luciferase activity of the MIR155HG-WT reporter vector but not MIR155HG-MUT reporter vector in HPMECs ( Figure 3B). However, miR-218-5p inhibitor transfection enhanced the luciferase activity

This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059. Four weeks following treatment, RVSP was measured and all rats were sacrificed for histological study. There was no significant difference in SBP in any group two weeks following MCT administration. Nonetheless RVSP was significantly increased in the MCT group compared with the control group. At 6 weeks, ASA treatment remarkably attenuated MCT-induced increased RVSP, RV hypertrophy, and pulmonary artery remodeling compared with the MCT group. The density of pulmonary capillaries in ASA-treated rats was also dramatically increased. Treatment with ASA significantly inhibited the increased p-ERK1/2 and restored the impaired endothelial nitric oxide synthase (eNOS) in MCT-treated rats. This study demonstrated that ASA distinctively attenuates MCT-induced PAH by inhibition of the ERK1/2 signaling pathway.

The present study aimed to investigate the biological function of colon cancer-associated transcript 2 (CCAT2) in the occurrence and progression of non-small cell lung carcinoma (NSCLC) and its potential use in the early diagnosis and molecular-targeted therapy of NSCLC. The tumor tissues, para-carcinoma tissues and associated clinical data of 36 patients with NSCLC were collected in order to detect the expression of CCAT2 and assess the impact of factors including histopathological type, Tumor-Node-Metastasis stage and lymph node metastasis on CCAT2 expression. The lung cancer NCI-H1975 cell line was transfected with a small interfering RNA (siRNA) plasmid to determine the effect of si-CCAT2 on NSCLC proliferation, invasion and metastasis. The effect of si-CCAT2 on the expression of nuclear and cytoplasmic β-catenin protein in the lung cancer NCI-H1975 cell line was detected using western blot analysis. The expression levels of CCAT2 in the tumor tissues of patients with NSCLC were significantly higher than those in the normal para-carcinoma tissues (t=8.580, P<0.01). Subsequent to CCAT2 silencing, the proliferation and invasive abilities of NCI-H1975 cells were significantly decreased compared with control cells (P<0.05). In the si-CCAT2 group, the level of nuclear and cytoplasmic β-catenin proteins was decreased, and the activity of the Wnt signaling pathway was significantly inhibited compared with the control cells (P<0.01), and a synergistic effect was exerted with the Wnt signaling inhibitor FH535. CCAT2 may therefore promote the occurrence of NSCLC by regulating the Wnt/β-catenin signaling pathway.