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Cigarette smoking constitutes a major human health hazard because it is the most important risk factor for lung cancer. Although evidence for smoking-induced lung cancer in humans is strong, the molecular mechanisms by which smoking causes cancer remain to be established. In this investigation, we evaluated the roles of inflammation and the epithelial-mesenchymal transition (EMT) in cigarette smoke extract (CSE)-induced transformation of human bronchial epithelial (HBE) cells. The results showed that chronic exposure to CSE induced EMT and transformation of these cells. Activation of nuclear factor-κB (NF-κB) by CSE increased levels of the proinflammatory interleukin-6 (IL-6), and acute and chronic exposures to CSE caused decreases in miR-200c levels. By blocking NF-κB with Bay11-7082 and IL-6 with anti-IL-6 antibody and enhancement of IL-6 with human recombinant IL-6, we found that the NF-κB signal pathway was involved in CSE-induced increases of IL-6, which suppressed miR-200c expression and promoted EMT. Moreover, IL-6 was necessary for maintenance of CSE-induced transformation and for malignant progression of HBE cells. Finally, blocking of NF-κB with Bay11-7082 prevented CSE-induced EMT and malignant transformation due to decreases of E-cadherin and miR-200c and elevations of IL-6, N-cadherin, and vimentin. Thus, we have defined a link between inflammation and EMT, processes involved in the malignant transformation of cells caused by CSE. This link, mediated through miRNAs, establishes a mechanism for CSE-induced lung carcinogenesis.

Lung cancer is the leading cause of cancer mortality worldwide. A common interest in lung cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. There is increasing evidence that microRNAs (miRNAs) are involved in lung cancer. To explore new biomarkers of chemical exposure in risk assessment of chemical carcinogenesis and lung cancer, we analyzed miRNA expression profiles of human bronchial epithelial (HBE) cells malignantly transformed by arsenite. High-throughput microarray analysis showed that 51 miRNAs were differentially expressed in transformed HBE cells relative to normal HBE cells. In particular, miR-191 was up-regulated in transformed cells. In HBE cells, arsenite induced increases of miR-191 and WT1 levels, decreased BASP1 expression, and activated the Wnt/β-catenin pathway, effects that were blocked by miR-191 knockdown. In addition, a luciferase reporter assay indicated that BASP1 is a direct target of miR-191. By inhibiting the expression of BASP1, miR-191 increased the expression of WT1 to promote activation of Wnt/β-catenin pathway. In transformed cells, inhibition of miR-191 expression blocked the epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties of cells and decreased their migratory capacity and neoplastic properties. Thus, these results demonstrate that miR-191 modulates the EMT and the CSC-like properties of transformed cells and indicate that it is an onco-miR involved in the neoplastic and metastatic properties of transformed cells.

BackgroundThe objectives of this study are to investigate the incidence and reporting behavior of sharp injuries among healthcare workers (HCWs) and identify the risk factors associated with these injuries.MethodsA cross-sectional survey was conducted in February 2017 in a provincial teaching hospital in China. Data were collected from 901 HCWs using a self-administered questionnaire which included demographic information, experience, and reporting behavior of sharp injuries. Stepwise logistical regression was used to analyze the risk factors.ResultsHCWs (248 [27.5%]) had sustained a sharp injury in the previous year. Factors including seniority, job category, title, education, department, and training programs were associated with the occurrence of sharp injuries. According to the stepwise logistical regression, seniority, and training programs were the risk factors associated with the occurrence of sharp injuries. Of 248 sharp injuries, 130 HCWs were exposed to blood. Only 44 (33.9%) HCWs reported their injuries to the concerned body. The main reasons for not reporting the sharp injuries were as follows: perception that the extent of the injury was light (30.2%), having antibodies (27.9%), and unaware of injury (16.3%).ConclusionsSharp injuries in the studied hospital were common and were likely to be underreported. Therefore, an effective reporting system and sufficient education on occupational safety should be implemented by the relevant institutions. Moreover, it is important to take effective measures to manage sharp injuries in HCWs and provide guidance for their prevention.