MiR-30a inhibits silica dust-induced epithelial-mesenchymal transition by targeting Snail.

The mechanism of action of MicroRNA-30a(miR-30a) and Snail, a transcription factor, in silica(SiO2) dust-induced pulmonary EMT and secondary pulmonary fibrosis remains elusive. In this study, the cellular EMT model induced by the stimulation of A549 cells with SiO2 was established. A549 cells were transfected with miR-30a mimic and miR-30a inhibitor and the SNAIL gene was silenced to examine the mechanism of miR-30a targeting Snail to regulate silica dust-induced EMT. The results showed that 50 μg/mL SiO2 stained A549 cells for 24 h could induce EMT in A549 cells. Exposure of A549 cells to SiO2 dust decreased miR-30a expression, as well as mRNA and protein expression levels of E-cad. Conversely, SiO2 exposure increased mRNA and protein expression levels of α-SMA, vimentin, and Snail. The miR-30a mimic upregulated mRNA and protein expression levels of E-cadherin in SiO2-induced A549 cells, while downregulating mRNA and protein expression levels of α-SMA, vimentin and Snail. MiR-30a inhibitors have the opposite effect. Silencing the SNAIL gene, followed by SiO2 dust-induced stimulation of A549 cells, could enhance mRNA and protein expression levels of E-cad, whereas those of α-SMA and vimentin were reduced. Altogether, we found that miR-30a directly targeted Snail and inhibited its expression, thereby delaying silica induced pulmonary EMT.

Huang F ，Li Y ，Guan L ，Hu Y ，Zeng M ... -  《-》

MiR-30 suppresses lung cancer cell 95D epithelial mesenchymal transition and invasion through targeted regulating Snail.

Fan MJ ，Zhong YH ，Shen W ，Yuan KF ，Zhao GH ，Zhang Y ，Wang SK ... -  《-》

MicroRNA-30a Suppresses the Activation of Hepatic Stellate Cells by Inhibiting Epithelial-to-Mesenchymal Transition.

The activation of hepatic stellate cells (HSCs) is considered as a pivotal event in liver fibrosis and epithelial-mesenchymal transition (EMT) process has been reported to be involved in HSC activation. It is known that microRNAs (miRNAs) play a pro-fibrotic or anti-fibrotic role in HSC activation. Recently, emerging studies show that miR-30a is down-regulated in human cancers and over-expression of miR-30a inhibits tumor growth and invasion via suppressing EMT process. However, whether miR-30a could regulate EMT process in HSC activation is still unclear. miR-30a expression was quantified using real-time PCR in carbon tetrachloride (CCl4)-induced rat liver fibrosis, activated HSCs and patients with cirrhosis. Roles of miR-30a in liver fibrosis in vivo and in vitro were also analyzed. Luciferase activity assays were performed to examine the binding of miR-30a to the 3'-untranslated region of snail family transcriptional repressor 1 (Snai1). miR-30a was down-regulated in human cirrhotic tissues. In CCl4 rats, reduced miR-30a was found in fibrotic liver tissues as well as isolated HSCs. There was a significant reduction in miR-30a in primary HSCs during culture days. miR-30a over-expression resulted in the suppression of CCl4-induced liver fibrosis. Restoration of miR-30a led to the inhibition of HSC activation including cell proliferation, α-SMA and collagen expression. Notably, miR-30a inhibited EMT process, with a reduction in TGF-β1 and Vimentin as well as an increase in GFAP and E-cadherin. miR-30a induced a significant reduction in Snai1 protein expression when compared with the control. Interestingly, Snail protein expression was increased during liver fibrosis, indicating that there may be a negative correlation between miR-30a level and Snai1 protein expression. Further studies demonstrated that Snai1 was a target of miR-30a. Our results suggest that miR-30a inhibits EMT process, at least in part, via reduction of Snai1, leading to the suppression of HSC activation in liver fibrosis.

Zheng J ，Wang W ，Yu F ，Dong P ，Chen B ，Zhou MT ... -  《-》

AEG-1 3'-untranslated region functions as a ceRNA in inducing epithelial-mesenchymal transition of human non-small cell lung cancer by regulating miR-30a activity.

Competitive endogenous messenger RNA regulates the transcription of other RNA moleculars through competing for the shared microRNAs. This study was carried out to explore the regulation of AEG-1 messenger RNA as a competitive endogenous RNA in the epithelial-mesenchymal transition and metastasis of lung tumor cells. It is shown that the epithelial-mesenchymal transition was associated with the down-regulation of miR-30a, up-regulation of AEG-1 and mesenchymal markers (Snail and Vimentin); miR-30a inhibited the metastasis of lung tumor A549 cells in vitro, whereas AEG-1 promoted it. These results suggested the potential linkage between miR-30a and genes (AEG-1, Snail and Vimentin) in the epithelial-mesenchymal transition and metastasis of lung tumor cell. It was verified later that the 3'-untranslated regions of AEG-1, Snail and Vimentin bind to miR-30a in A549 cells. Therefore, a competitive endogenous RNAs regulatory network among AEG-1, Snail and Vimentin mediated via competitive binding to miR-30a was proved. That is, the 3'-untranslated region of AEG-1, functioning as the competitive endogenous RNAs, indirectly regulated the expression of Vimentin and Snail in inducing epithelial-mesenchymal transition of human non-small cell lung cancer. In conclusion, our findings demonstrated a competitive endogenous RNAs regulatory network which will help understand the metastasis mechanisms of lung cancer and improve the prevention and treatment of lung cancer.

Liu K ，Guo L ，Guo Y ，Zhou B ，Li T ，Yang H ，Yin R ，Xi T ... -  《-》

miR-138 inhibits epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by regulating ZEB2.

Silica dust is a common pollutant in the occupational environment, such as coal mines. Inhalation of silica dust can cause progressive pulmonary fibrosis and then silicosis. Silicosis is still one of the most harmful occupational diseases in the world, so the study of its pathogenesis is necessary for the treatment of silicosis. In this study, we constructed a mouse model of pulmonary fibrosis via intratracheal instillation of silica particles and identified the decreased expression of miR-138 in fibrotic lung tissues of mice. Moreover, the overexpression of miR-138 retarded the process of epithelial-mesenchymal transition (EMT) in a mouse model of silica particles exposure and epithelial cells stimulated by silica particles. Further studies showed that ZEB2 was one of the potential targets of miR-138, and the up-regulation of miR-138 reduced ZEB2 levels in mouse lung tissues and in epithelial cells. We next found that the expression levels of ɑ-SMA and Vimentin were significantly increased and E-cadherin levels were decreased after transfection with miR-138 inhibitor in epithelial cells. However, these effects were abated by the knockdown of ZEB2. Consistently, the increased migration ability of epithelial cells by miR-138 inhibitor transfection was also reversed by the knockdown of ZEB2. Collectively, we revealed that miR-138 significantly targeted ZEB2, thus inhibited the EMT process and mitigated the development of pulmonary fibrosis. miR-138 may be a potential target for the treatment of pulmonary fibrosis.

Wu Q ，Gui W ，Jiao B ，Han L ，Wang F ... -  《-》