No abstract

Edited by Tamas DalmayKeywords: miR-134 Epithelial-to-mesenchymal transition (EMT) NSCLC FOXM1 TGF-b1 a b s t r a c t Recent studies have implied that miRNAs act as crucial modulators for epithelial-to-mesenchymal transition (EMT). We found that miR-134 expression correlated with invasive potential and EMT phenotype of NSCLC cells. Functional assays demonstrated that miR-134 inhibited EMT in NSCLC cells. In addition, we showed that Forkhead Box M1 (FOXM1) is a direct target of miR-134. Knockdown of FOXM1 reversed EMT resembling that of miR-134 overexpression. We further found that FOXM1 was involved in TGF-b1-induced EMT in A549 cells. These findings suggest that miR-134 acts as a novel EMT suppressor in NSCLC cells.

An imbalance of circulating Th17 cells and Tregs is associated with the deterioration of pulmonary function in patients with moderate and severe COPD.

The NLR pyrin domain-containing protein 3 (NLRP3) inflammasome, a multi-protein complex, produces the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, which may contribute to the development of airway inflammation in chronic obstructive pulmonary disease (COPD). The aim of this study was to explore the correlation between circulating and local airway NLRP3 inflammasome activation with acute exacerbation of COPD (AECOPD). mRNA levels of NLRP3, Caspase (Casp)-1, apoptosis-associated speck-like protein containing CARD (ASC), IL-18, and IL-1β in peripheral blood mononuclear cells (PBMCs) and bronchial tissues were determined by real-time PCR in 32 smokers, 65 patients with AECOPD, 50 COPD patients in recovery stage, and 30 COPD patients in stable stage. The levels of IL-1β and IL-18 in serum and bronchoalveolar lavage fluid (BALF) supernatants were measured by ELISA. The load of six common pathogens in BALF samples were determined by real-time PCR. The potential correlation between the mRNA levels of NLRP3, Casp-1, ASC, IL-18 or IL-1β and the load of pathogens was evaluated individually. Significantly higher mRNA levels of NLRP3, Casp-1, ASC, IL-18, IL-1β and higher levels of IL-18 and IL-1β were found in patients with AECOPD than in smokers. These NLRP3 inflammasome mediators were significantly decreased when COPD patients in the same group became clinical stable. The increased mRNA levels of NLRP3 inflammasomes in bronchial tissues were positively correlated with the load of the six common pathogens in the lower respiratory tract. We conclude that systemic and local airway NLRP3 inflammasome activation is associated with the acute exacerbation, which might be predictive factors of the acute exacerbation and clinical outcomes in COPD patients.

BackgroundMicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood.MethodsWe detected miR-27a expression in two lung adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects of miR-27a on the metastasis and the chemosensitivity of cancer cells, using both gain- and loss-of-function studies. The correlation between miR-27a level and chemoresistance was further investigated in clinical lung adenocarcinoma specimens.ResultsmiR-27a was significantly up-regulated in cisplatin-resistant lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-27a regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo. Further studies identified Raf Kinase Inhibitory Protein (RKIP) as a direct and functional target of miR-27a. Small interfering RNA-mediated RKIP knockdown revealed similar effects as that of ectopic miR-27a expression, while overexpression of RKIP attenuated the function of miR-27a in lung adenocarcinoma cells. Increased miR-27a expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and was proved to be correlated with low expression of RKIP, decreased sensitivity to cisplatin, and poor prognosis.ConclusionOur results suggest that up-regulation of miR-27a could suppress RKIP expression and in turn contribute to chemoresistance of lung adenocarcinoma cells to cisplatin.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-193) contains supplementary material, which is available to authorized users.

Recent studies have implied that miRNAs act as crucial modulators for epithelial-to-mesenchymal transition (EMT). We found that miR-148a is significantly downregulated in non-small cell lung cancer (NSCLC) compared to adjacent non-cancerous lung tissues, and the downregulated miR-148a was significantly associated with lymph-node metastasis. Functional assays demonstrated that miR-148a inhibited EMT in NSCLC cells. Moreover, miR-148a decreased 3'-untranslated region luciferase activity of ROCK1 and ROCK1 protein expression. Knockdown of ROCK1 reversed EMT resembling that of miR-148a overexpression. Furthermore, ROCK1 was widely upregulated in NSCLC, and its mRNA levels were inversely correlated with miR-148a expression. These findings suggest that miR-148a acts as a novel EMT suppressor in NSCLC cells, at least in part by modulation of ROCK1.

No abstract

Long non-coding RNAs have been implicated in human cancer but their mechanisms of action are mainly undocumented. In this study, we found that HOXA11-AS expression was upregulated in non-small cell lung cancer tissues and cell lines. High levels of HOXA11-AS expression were correlated with larger tumor size and lymph node metastasis. Functional analysis revealed that HOXA11-AS promotes non-small cell lung cancer cell proliferation and invasion. In particular, HOXA11-AS functions as a competing endogenous RNA to regulate transcriptional factor Sp1 expression via sponging miR-124. Collectively, our findings reveal an oncogenic role for HOXA11-AS in non-small cell lung cancer tumorigenesis.