Pixin Ran, Nanshan Zhong, and colleagues report that cleaner cooking fuels and improved ventilation were associated with better lung function and reduced COPD among a cohort of villagers in Southern China. Please see later in the article for the Editors' Summary

Epithelial-mesenchymal transition (EMT) has been proposed to be a mechanism in airway remodeling, which is a characteristic of chronic obstructive pulmonary disease (COPD). Studies have shown that cigarette smoke and nicotine are factors that induce Wnt/β-catenin activation, which is a pathway that has also been implicated in EMT. The main aim of this study was to test whether human bronchial epithelial cells are able to undergo EMT in vitro following nicotine stimulation via the Wnt3a/β-catenin signaling pathway. We show that nicotine activates the Wnt3a signal pathway, which leads to the translocation of β-catenin into the nucleus and activation of β-catenin/Tcf-dependent transcription in the human bronchial epithelial cell (HBEC) line. This accumulation was accompanied by an increase in smooth muscle actin, vimentin, matrix metalloproteinases-9, and type I collagen expression as well as downregulation of E-cadherin, which are typical characteristics of EMT. We also noted that the release of TGF-β(1) from these cells was stimulated by nicotine. Knockdown of Wnt3a with small interfering RNA (siRNA) prevented these effects, implying that β-catenin activation in these responses is Wnt3a dependent. Furthermore, specific knockdown of TGF-β(1) with TGF-β(1) siRNA partially prevented nicotine-induced EMT, suggesting that TGF-β(1) has a role in nicotine-mediated EMT in HBECs. These results suggest that HBECs are able to undergo EMT in vitro upon nicotine stimulation via the Wnt3a/β-catenin signaling pathway.

This study was to investigate the expression correlation between long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1), miR-200a-3p and programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), and their roles in NSCLC. Real-time polymerase chain reaction (PCR) was performed to detect the expressions of MALAT1, miR-200a-3p and PD-L1 in NSCLC tissues and cells for the correlation analysis. The starBase and Targetscan databases were used to predict the binding sites between MALAT1 and miR-200a-3p, and miR-200a-3p and PD-L1, respectively. The targeting relationship between MALAT1 and miR-200a-3p, and miR-200a-3p and PD-L1 were further verified by real-time PCR and dual luciferase reporter gene assay. Cell proliferation was monitored by CCK8 and colony formation assays. The apoptosis was detected using flow cytometry. Wound healing assay and transwell assay were conducted to determine cell migration and invasion. In this study, we demonstrated that in NSCLC tissues, the expression level of MALAT1 was negatively correlated with that of miR-200a-3p, while positively correlated with PD-L1. Besides, MALAT1 promoted proliferation, mobility, migration, and invasion of NSCLC cells via sponging miR-200a-3p. PD-L1 was validated as a target of miR-200a-3p, and indirectly modulated by MALAT1. In conclusion, LncRNA MALAT1 facilitates the progression of NSCLC by modulating miR-200a-3p/PDL1 axis.