Increasing evidence has revealed that aberrant expression of miRNAs contributes to non-small cell lung cancer (NSCLC) development and progression. However, the roles and mechanisms of various miRNAs in NSCLC remain to be determined. In the present study, we confirmed that reduced miR-212 expression was present in NSCLC tissues and cell lines. Our clinical analysis revealed that the reduced miR-212 expression was significantly correlated with poor prognostic features including positive lymph node metastasis and advanced tumor-node-metastasis (TNM) stage. Moreover, we demonstrated that miR-212 is a novel independent prognostic marker for predicting 5-year survival of NSCLC patients. The ectopic overexpression of miR-212 inhibited cell migration, invasion and EMT, while downregulated miR-212 reversed the effect. In addition, miR-212 regulated SOX4 by directly binding to its 3'-untranslated region (3'-UTR), leading to suppression of EMT progression. In clinical samples of NSCLC, miR-212 was negatively correlated with SOX4, which was upregulated in NSCLC. Alteration in SOX4 expression reversed the functional effects of miR-212 in regards to migration, invasion and EMT in the NSCLC cells. In conclusion, our data indicated that miR-212 functions as a tumor-suppressor gene by regulating EMT and metastasis of NSCLC by targeting SOX4 signaling, and may represent a novel potential therapeutic target and prognostic marker for NSCLC.

Asthma, characterized by dysfunction of airway epithelial cells, is regarded as a chronic inflammatory disorder in the airway. Ubiquitin-specific protease 8 (USP8) belongs to ubiquitin proteasome system and mediates the stability of E3 ligases. The anti-inflammatory effect of USP8 has been widely investigated in distinct diseases, while the role of USP8 in asthma remains elusive. Firstly, human bronchial epithelial cells (BEAS-2B) were treated with lipopolysaccharide, which reduced the cell viability of BEAS-2B and induced the secretion of lactate dehydrogenase (LDH). Moreover, the expression of USP8 was downregulated in BEAS-2B post lipopolysaccharide treatment. Secondly, overexpression of USP8 enhanced cell viability of lipopolysaccharide-treated BEAS-2B, and reduced the LDH secretion. USP8 overexpression also attenuated lipopolysaccharide-induced upregulation of TNF-α, IL-6, and IL-1β in BEAS-2B. Thirdly, lipopolysaccharide treatment promoted the expression of NLRP3 (NLR Family Pyrin Domain Containing 3), N-terminal domain of gasdermin D (GSDMD-N), caspase-1, IL-1β, and IL-18 in BEAS-2B, which was inhibited by USP8 overexpression. Lastly, USP8 overexpression decreased the phosphorylation of NF-κB, while it increased the phosphorylation of PI3K and AKT in lipopolysaccharide-treated BEAS-2B. In conclusion, USP8 inhibited lipopolysaccharide-triggered inflammation and pyroptosis in human bronchial epithelial cells by activating PI3K/AKT signaling and inhibiting NF-κB signaling pathway.