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Abstract Background The aim of the study was to measure the expression of microRNA (miR)-181b in patients with lung cancer, investigate its biological function and elucidate the underlying mechanisms associated with the development of lung cancer. Methods miR-181b expression in tissues was measured via RT-qPCR. After A549 cells were transfected with miR-181b mimic or si-Sox6, the proliferation, migration and cell cycle distribution of A549 were evaluated using cell counting kit-8 assay, transwell assay and flow cytometry. The levels of cell cycle-related proteins and Sox6 were analyzed by western blotting. Gene targets of miR-181b were predicted via bioinformatics analysis and verified using a dual-luciferase reporter gene assay. Results Expression of miR-181b was significantly downregulated in lung cancer tissues (P < 0.05), and was inversely correlated with the degree of cell differentiation and clinical stages of lung cancer (both P < 0.05). Additionally, the expression of miR-181b was significantly lower in adenocarcinoma compared with squamous cell carcinoma in the lungs (P < 0.05). Overexpression of miR-181b significantly decreased the protein level of Sox6 and significantly suppressed the cell proliferation and metastasis (both P < 0.05); this effect was also observed in A549 cells transfected with si-Sox6. The luciferase activity of a Sox6 3′-untranslated region-based reporter construct was significantly lower when transfected with miR-181b (P < 0.05), which suggests that Sox6 is a direct target of miR-181b. Conclusion The results of the present study suggest that miR-181b may function as a tumor inhibitor in the development of lung cancer via targeting Sox6 to decrease the proliferation and metastasis of lung cancer cells. [ABSTRACT FROM AUTHOR]

The expression of microRNA-181b (miR-181b) has been investigated in various human cancers. However, the expression and functions of miR-181b in non-small cell lung cancer (NSCLC) are yet to be studied. In the present study, miR-181b expression in NSCLC tissues and cell lines was analyzed by quantitative polymerase chain reaction, and was shown to be recurrently downregulated. Following transfection of the H23 and H522 NSCLC cells lines with miR-181b, cell migration and cell invasion assays were performed to evaluate the effect of miR-181b overexpression on the cell motility. It was demonstrated that overexpression of miR-181b inhibited the migration and invasion of NSCLC cells. Subsequently, bioinformatics analysis, western blotting and luciferase reporter assays were conducted to investigate the mechanism underlying the miR-181b-mediated inhibition of NSCLC cell motility. It was found that miR-181b directly targeted high-mobility group box-1 (HMGB1) in NSCLC cells. These results reveal a novel therapeutic target, the miR-181b/HMGB1 axis, in NSCLC. Treatment approaches targeting this axis will be beneficial to prevent NSCLC from becoming invasive. [ABSTRACT FROM AUTHOR]

Background: Lung cancer stem cells have the ability to self-renew and are resistant to conventional chemotherapy. MicroRNAs (miRNAs) regulate and control the expression and function of many target genes; therefore, miRNA disorders are involved in the pathogenesis of human diseases, such as cancer. However, the effects of miRNA dysregulation on tumour stemness and drug resistance have not been fully elucidated. miR-181b has been reported to be a tumour suppressor miRNA and is associated with drug-resistant non-small cell lung cancer. Methods: Cancer stem cell (CSC)-like properties were tested by a cell proliferation assay and flow cytometry; miR-181b expression was measured by real-time PCR; and Notch2 and related proteins were detected by Western blotting and immunohistochemistry. A mouse xenograft model was also established. Results: In this study, we found that ectopic miR-181b expression suppressed cancer stem cell properties and enhanced sensitivity to cisplatin (DDP) treatment by directly targeting Notch2. miR-181b could inactivate the Notch2/Hes1 signalling pathway. In addition, tumours from nude mice treated with miR-181b were significantly smaller than tumours from mice treated with control agomir. Decreased miR-181b expression and increased Notch2 expression were observed to have a significant relationship with overall survival (OS) and CSC-like properties in non-small cell lung cancer (NSCLC) patients. Conclusions: This study elucidates an important role of miR-181b in the regulation of CSC-like properties, suggesting a potential therapeutic target for overcoming drug resistance in NSCLC. [ABSTRACT FROM AUTHOR]