In summary, results suggest hsa_circ_0007385 plays a role in NSCLC tumorigenesis, providing a potential therapeutic target for NSCLC.

AWPPH is a newly discovered long non-coding (lnc)RNA that serves an oncogenic role in the development of several types of cancer; however, its involvement in non-small cell lung cancer (NSCLC) is unknown. Therefore, the aim of the present study was to investigate the function of AWPPH in NSCLC. The results demonstrated that AWPPH expression levels were significantly upregulated in the lung tissues and serum samples of patients with NSCLC compared with in healthy controls. High expression levels of AWPPH effectively distinguished NSCLC patients from healthy controls. In addition, patients with high expression levels of AWPPH had significantly shorter survival time. AWPPH overexpression in NSCLC cells promoted proliferation and inhibited apoptosis, and activated the Wnt/β-catenin signaling pathway, which is a classic signaling pathway involved in the development and progression of different types of cancers. Treatment with a Wnt/β-catenin signaling pathway activator produced no significant effect on AWPPH expression. Therefore, it was concluded that lcRNA AWPPH could promote the growth of NSCLCs by activating the Wnt/β-catenin signaling pathway.

What is the central question of this study? Airway angiogenesis occurs in asthma, and airway smooth muscle (ASM) cells have been reported to be capable of promoting airway angiogenesis. What is the potential mechanism by which ASM cells harvested from patients with asthma are capable of promoting airway angiogenesis? What is the main finding and its importance? Endogenous STAT3 mediated the pro-angiogenic ability of ASM cells by directly activating VEGF signalling. These findings contribute to the understanding of airway angiogenesis in pathology and could represent a possible therapeutic target for asthma. Airway angiogenesis indicates the specific vascular structure remodelling that occurs in asthma. Airway smooth muscle (ASM) cells have been reported to be capable of promoting airway angiogenesis; however, the potential mechanism is not yet fully defined. Herein, we investigated the role of signal transducer and activator of transcription 3 (STAT3) in the progress of airway angiogenesis. Western blot analysis showed that STAT3 activation was aberrantly upregulated in ASM tissues of patients with asthma and ASM cells that were exposed to cytokines to imitate the airway conditions in patients with asthma. Compared with the control group, both the inhibition of STAT3 activation and the silencing of endogenous STAT3 in ASM cells significantly reduced the proliferation, migration and tube-forming ability of human lung microvascular endothelial cells induced by the conditioned medium (CM) of ASM cells. The increased proliferation and migration of human aortic vascular smooth muscle cells were also repressed by inhibition of STAT3 in ASM cells. Besides, the increased activity of VEGF signalling was observed in ASM cells and the CM by RT-PCR and Western blotting assay, whereas this increased activity was reduced by STAT3 silencing. Further studies indicated that STAT3 regulated VEGF activation by directly interacting with the binding site on the 5' region of the VEGF gene. The increase in STAT3-induced pro-angiogenic activity of ASM cells was significantly decreased by administration of VEGF neutralizing antibody. In conclusion, we provided evidence that endogenous STAT3 mediates the pro-angiogenic ability of ASM cells by directly activating VEGF signalling, which could represent a possible therapeutic target for asthma.

COPD, or Chronic obstructive pulmonary disease, is an inflammation-related disease and lead to cachexia and muscle wasting. Altered nuclear factor erythroid 2-related factor 2 (Nrf2) expression is found in patients of COPD because it is involved in pulmonary protective effects. MiR-29b could be activated by Nrf2. We hypothesized that miR-29b might mediate the regulation of Nrf2 on Th1/Th2 differentiation and airway epithelial remodeling in COPD rats. SD rats were exposed to smoke for COPD induction. Expression of Nrf2 mRNA and miR-29b in lung tissues was quantified. Expression of Nrf2 and matrix metalloproteinase 2 (MMP2) were also detected by immunohistochemistry and western blot. Th1 markers and Th2 markers were measured by ELISA in peripheral blood. Flow cytometry was used to detect the Th1/Th2 ratio. miR-29b and Nrf2 was manipulated at mRNA level in A549 cells using transfection. Cellular growth and migration were measured in transfectants. In lung tissues of COPD rats, expression of Nrf2 and miR-29b decreased. MMP2, a target of miR-29b, had an opposite expression to miR-29b in peripheral blood. Levels of inflammatory factors and Th1/Th2 ratio increased. MiR-29b mediated the regulation of Nrf2 on remodeling of lung epithelial cells. Blocking Nrf2 expression in A549 cells led to the opposite expression of miR-29b and further decreased MMP2 production; meanwhile, cell growth and motility were improved. Different miR-29b levels affected MMP2 expression and cellular characteristics. The findings suggested that miR-29b was a regulator the pathological progress of COPD. It mediates the effect of Nrf2 on Th1/Th2 differentiation and on remodeling process of airway epithelial cells.

Claudin-1 (CLDN-1) is one of main tight junction components that play an important role in epithelial-mesenchymal transition (EMT). However, the effects of CLDN-1 on the migration and EMT induced by TGF-β1 in primary normal human bronchial epithelial (NHBE) and BEAS-2B cells have not been clear. The expression of CLDN-1 was quantified by Western blotting in NHBE and BEAS-2B cells. Cell migration and invasion were detected using transwell assays. The expression level of E-cadherin, N-cadherin, α-SMA, and Vimentin was evaluated by quantitative real-time PCR and Western blotting. Here we showed that the protein expression of CLDN-1 was increased exposed to TGF-β1 in a dose- and time-dependent manner. Knockdown of CLDN-1 using small interfering CLDN-1 RNA (siCLDN-1) prevented the migration and invasion in NHBE and BEAS-2B cells. Moreover, depletion of CLDN-1 promoted the E-cadherin expression and decreased the mRNA and protein levels of N-cadherin, α-SMA, and Vimentin induced by TGF-β1. Furthermore, CLDN-1 silencing resulted in the reduction of the Notch intracellular domain (NICD) and hairy enhancer of split-1 (Hes-1) in mRNA and protein level. Jagged-1, an activator of Notch signaling pathway, abrogated the protective function of siCLDN-1 in migration and EMT. In conclusion, CLDN-1 promoted the migration and EMT through the Notch signaling pathway.