Lung cancer is an significant cause of death worldwide, and non–small‐cell lung cancer (NSCLC) is the most common type of lung cancer. MicroRNAs (miRNAs) have been identified to play key roles in NSCLC development. Recently, it has been reported that miR‐605‐5p is a cancer‐related miRNA in several types of tumors. In this study, we study the role of miR‐605‐5p in NSCLC cells. We find that miR‐605‐5p is upregulated in NSCLC cells. Overexpression of miR‐605‐5p significantly promotes lung cancer invasion and migration in H460 and H1299 cells. Besides this, miR‐605‐5p also promotes lung cancer cell carcinoma proliferation and metastasis in vivo. However, downregulation of miR‐605‐5p inhibits cell invasion and migration by inhibiting lung cancer cell carcinoma proliferation and metastasis. In addition, the luciferase report assay identifies 3′‐untranslated region tumor necrosis factor α‐induced protein 3 (TNFAIP3) as a target of miR‐605‐5p. Silencing of TNFAIP3 promotes invasion and proliferation in lung cancer. In addition, the knockdown of TNFAIP3 restores the significant decrease in invasion and proliferation in miR‐605‐5p‐inhibitor–transfected lung cancer cells. In conclusion, miR‐605‐5p promotes invasion and proliferation by targeting TNFAIP3 in NSCLC, and may provide possible biomarkers for NSCLC therapy.
Background: Nuclear factor erythroid 2-related factor 2 (Nrf2) protects the lung from sepsis-induced injury through activating Nrf2-regulated multiple phase 2 detoxification genes, including NAD(P)H: quinine oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO1). Based on the positive effect of Sirtuin 6 on Nrf2, we aim to explore the potential role of SIRT6 in the mechanism of sepsis-induced acute lung injury (ALI).Methods: Mouse models of sepsis were constructed by instilling intratracheal of lipopolysaccharide (LPS; 4 ml/kg). After 48-hour treatment, lung tissues were collected to measure the degree of lung injury. The SIRT6, siSIRT6, and siNrf2 plasmids were cotransfected into various concentrations of LPS-treated human umbilical vein endothelial cells (HUVECs; 0, 1, 5, 10, and 50 μg/ml) using Lipofectamine 2000. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay. Expression levels of SIRT6, Nrf2, NQO1, and HO1 was measured by quantitative polymerase chain reaction and Western blot analysis. Cell apoptosis was determined by flow cytometry. Results: Lung tissues in the model group already had basic characteristics of ALI.Compared with the control model, TNF-α and IL-6 levels were much higher (P < 0.01), the levels of SIRT6, Nrf2, and Nrf2-modulated detoxification factors were downregulated (P < 0.01). SIRT6 overexpression decreased the apoptosis below to 10% (P < 0.01), significantly increased the Nrf2 expression, effectively inhibited TNFα and IL-6 releases, and enhanced NQO1 and HO1 levels (P < 0.01). siNrf2 abolished the protective effects of SIRT6 overexpression, including increasing apoptosis and inhibiting anti-inflammatory and antioxidative genes expressions (P < 0.01). Conclusions: Our study suggested SIRT6 positively regulated Nrf2 expression and activated Nrf2-regulated anti-inflammatory and antioxidative enzymes, which could effectively mitigate LPS-induced HUVECs inflammatory responses. This might reflect the mechanism of ALI induced by sepsis.
K E Y W O R D Sheme oxygenase-1, inflammatory cytokines, NAD(P)H: quinine oxidoreductase-1, oxidative stress
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