Extracellular Adenosine Diphosphate Stimulates CXCL10-Mediated Mast Cell Infiltration Through P2Y1 Receptor to Aggravate Airway Inflammation in Asthmatic Mice.

Asthma is an inflammatory disease associated with variable airflow obstruction and airway inflammation. This study aimed to explore the role and mechanism of extracellular adenosine diphosphate (ADP) in the occurrence of airway inflammation in asthma. The expression of ADP in broncho-alveolar lavage fluid (BALF) of asthmatic patients was determined by enzyme linked immunosorbent assay (ELISA) and the expression of P2Y1 receptor in lung tissues was determined by reverse transcription-quantitative polymerase chain reaction. Asthmatic mouse model was induced using ovalbumin and the mice were treated with ADP to assess its effects on the airway inflammation and infiltration of mast cells (MCs). Additionally, alveolar epithelial cells were stimulated with ADP, and the levels of interleukin-13 (IL-13) and C-X-C motif chemokine ligand 10 (CXCL10) were measured by ELISA. We finally analyzed involvement of NF-κB signaling pathway in the release of CXCL10 in ADP-stimulated alveolar epithelial cells. The extracellular ADP was enriched in BALF of asthmatic patients, and P2Y1 receptor is highly expressed in lung tissues of asthmatic patients. In the OVA-induced asthma model, extracellular ADP aggravated airway inflammation and induced MC infiltration. Furthermore, ADP stimulated alveolar epithelial cells to secrete chemokine CXCL10 by activating P2Y1 receptor, whereby promoting asthma airway inflammation. Additionally, ADP activated the NF-κB signaling pathway to promote CXCL10 release. As a "danger signal" extracellular ADP could trigger and maintain airway inflammation in asthma by activating P2Y1 receptor. This study highlights the extracellular ADP as a promising anti-inflammatory target for the treatment of asthma.

LncRNA BLACAT1 is involved in chemoresistance of non­small cell lung cancer cells by regulating autophagy.

The aim of the present study was to determine the effect of the long non­coding RNA (lncRNA) bladder cancer­associated transcript 1 (BLACAT1) in chemoresistance of non­small cell lung cancer (NSCLC) cells. Expression of lncRNA BLACAT1, microRNA (miR)­17, autophagy­related protein 7 (ATG7), multidrug­resistance protein 1 (MRP1), and the autophagy­associated proteins light chain 3 (LC3)­II/LC3­I and Beclin 1 were detected using the reverse transcription­quantitative polymerase chain reaction and western blot analysis. Cell viability was determined using an MTT assay. The interaction between BLACAT1 and miR­17 was determined using RNA immunoprecipitation and RNA pull­down assays. A cisplatin (DDP)­resistant NSCLC cell A549/DDP xenograft model in nude mice was established to investigate the effect of BLACAT1 on the chemoresistance of NSCLC cells. Compared with in DDP­sensitive NSCLC cells, expression of BLACAT1, ATG7, MRP1, LC3­II/LC3­I and Beclin 1 was significantly upregulated in DDP­resistant NSCLC cells, whereas miR­17 was downregulated in DDP­resistant NSCLC cells. Short interfering RNA against BLACAT1 decreased the viability of DDP­resistant NSCLC cells. In addition, BLACAT1 interacted with miR­17, and negatively regulated miR­17. BLACAT1 promoted ATG7 expression through miR­17, and facilitated autophagy and promoted chemoresistance of NSCLC cells through miR­17/ATG7. Finally, in vivo experiments indicated that inhibition of BLACAT1 ameliorated the chemoresistance of NSCLC. BLACAT1 was upregulated in DDP­resistant NSCLC cells, and promoted autophagy and chemoresistance of NSCLC cells through the miR­17/ATG7 signaling pathway.

MiR-449c targets c-Myc and inhibits NSCLC cell progression.

MicroRNAs (miRNA) play an important role in tumorigenesis, proliferation, and differentiation. Altered miRNA expression in cancer indicates that miRNAs can function as tumor suppressors or oncogenes. MiR-449c downregulation in non-small cell lung cancer (NSCLC) compared with normal lung tissues was investigated in this study. NSCLC cell proliferation and invasion assays indicate that transfection of miR-449c expression plasmid inhibits the proliferation and invasion ability of NCI-H23 and NCI-H838 cells. In addition, miR-449c overexpression could suppress tumor growth in vivo. Morever, c-Myc was identified as a direct target gene of miR-449c. These findings clearly suggest that miR-449c downregulation and c-Myc amplification may be involved in the development of NSCLC.