A ferroptosis-related signature predicts the clinical diagnosis and prognosis, and associates with the immune microenvironment of lung cancer.

Targeting ferroptosis-related pathway is a potential strategy for treatment of lung cancer (LC). Consequently, exploration of ferroptosis-related markers is important for treating LC. We collected LC clinical data and mRNA expression profiles from TCGA and GEO database. Ferroptosis-related genes (FRGs) were obtained through FerrDB database. Expression analysis was performed to obtain differentially expressed FRGs. Diagnostic and prognostic models were constructed based on FRGs by LASSO regression, univariate, and multivariate Cox regression analysis, respectively. External verification cohorts GSE72094 and GSE157011 were used for validation. The interrelationship between prognostic risk scores based on FRGs and the tumor immune microenvironment was analyzed. Immunocytochemistry, Western blotting, and RT-qPCR detected the FRGs level. Eighteen FRGs were used for diagnostic models, 8 FRGs were used for prognostic models. The diagnostic model distinguished well between LC and normal samples in training and validation cohorts of TCGA. The prognostic models for TCGA, GSE72094, and GSE157011 cohorts significantly confirmed lower overall survival (OS) in high-risk group, which demonstrated excellent predictive properties of the survival model. Multivariate Cox regression analysis further confirmed risk score was an independent risk factor related with OS. Immunoassays revealed that in high-risk group, a significantly higher proportion of Macrophages_M0, Neutrophils, resting Natural killer cells and activated Mast cells and the level of B7H3, CD112, CD155, B7H5, and ICOSL were increased. In conclusion, diagnostic and prognostic models provided superior diagnostic and predictive power for LC and revealed a potential link between ferroptosis and TIME.

Exosome miR-101-3p derived from bone marrow mesenchymal stem cells promotes radiotherapy sensitivity in non-small cell lung cancer by regulating DNA damage repair and autophagy levels through EZH2.

BACKGROUND AND OBJECTIVE: The morbidity rate of non-small cell lung cancer (NSCLC) increases with age, highlighting that NSCLC is a serious threat to human health. The aim of this study was mainly to describe the role of exosomal miR-101-3p derived from bone marrow mesenchymal stem cells (BMSCs) in NSCLC. METHODS: A549 or NCI-H1703 cells (1×105/mouse) were injected into nude mice to establish an NSCLC animal model. RTqPCR, Western blotting and comet assays were used to assess the changes in gene expression, proteins and DNA damage repair. RESULTS: miR-101-3p and RAI2 were found to be expressed at low levels in NSCLC, while EZH2 was highly expressed. In terms of function, miR-101-3p downregulated EZH2. In addition, exosomal miR-101-3p derived from BMSCs promoted the expression of RAI2, inhibited DNA damage repair, and inhibited the activation of the PI3K/AKT/mTOR signaling pathway by inhibiting EZH2, thereby promoting autophagy and decreasing cell viability and finally enhancing the sensitivity of NSCLC to radiotherapy and inhibiting the malignant biological behavior of NSCLC. CONCLUSION: Exosomal miR-101-3p derived from BMSCs can inhibit DNA damage repair, promote autophagy, enhance the radiosensitivity of NSCLC, and inhibit the progression of NSCLC by inhibiting EZH2.

Taurine inhibits KDM3a production and microglia activation in lipopolysaccharide-treated mice and BV-2 cells.

Microglia activation has been suggested as the key factor in neuro-inflammation and thus participates in neurological diseases. Although taurine exhibits anti-inflammatory and neuro-protective effects, its underlying epigenetic mechanism is unknown. In this study, taurine was administered to lipopolysaccharide (LPS)-treated mice and BV-2 cells. Behavioral test, morphological analyze, detection of microglia activation, and lysine demethylase 3a (KDM3a) measurements were performed to investigate the mechanism by which taurine regulates KDM3a and subsequently antagonizes microglia activation. Taurine improved the sociability of LPS-treated mice, inhibited microglia activation in the hippocampus, and reduced generation of brain inflammatory factors, such as interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2. Meanwhile, taurine suppressed the LPS-induced increase in microglial KDM3a, and increased the level of mono-, di- or tri-methylation of lysine 9 on histone H3 (H3K9me1/2/3). Furthermore, taurine inhibited the LPS-induced increase in KDM3a, elevated the H3K9me1/2/3 level, and reduced inflammatory factors and reactive oxygen species in a concentration-dependent manner in LPS-stimulated BV-2 cells. In conclusion, taurine inhibited KDM3a and microglia activation, thereby playing an anti-inflammatory role in LPS-treated mice and BV-2 cells.