Inhibiting LCN2 can suppress the development of NSCLC by promoting ferroptosis.

BACKGROUND: Tumor progression is intricately linked to ferroptosis, a recently discovered form of regulated cell death. However, the specific causes of ferroptosis in non-small cell lung cancer (NSCLC) remain unclear. METHODS: In this study, we conducted transcriptome sequencing on NSCLC samples and identified Lipocalin-2 (LCN2) as a significantly differentially expressed gene associated with ferroptosis in NSCLC. Through the intersection of the set of significantly different genes with ferroptosis-related genes, we unveiled the relevance of LCN2 in NSCLC. To validate our findings, several cell lines (BEAS-2B, A549, H1299, PC-9, H1975) were utilized, and Western blot (WB) analysis was performed. We employed a variety of assays, including CCK8, EDU, scratch, Transwell, and specific assays targeting ferroptosis, to investigate the effects of LCN2 on NSCLC cell proliferation, migration, and ferroptosis. Additionally, LCN2 was evaluated in vivo using a mouse tumor xenograft model. RESULTS: In both NSCLC patients and cells, LCN2 exhibited upregulation and was associated with a poor prognosis. Inhibition of LCN2 promoted ferroptosis, resulting in the inhibition of NSCLC proliferation and migration. Conversely, the ferroptosis inhibitor Fer-1 promoted NSCLC cell proliferation and migration while inhibiting ferroptosis. Furthermore, down-regulating LCN2 reduced Fer-1's promotion of NSCLC cell migration and proliferation, as well as its prevention of ferroptosis. In vivo inhibition of LCN2 prevented NSCLC cell growth and enhanced ferroptosis. CONCLUSION: Based on our research, reducing LCN2 could effectively induce ferroptosis and hinder the growth of NSCLC.

Ratiometric electrochemical biosensor based on lateral movement of multi-pedal DNA tetrahedron machine on biomimetic interface.

In this work, a lateral moving multi-pedal DNA tetrahedron machine (MTM) is designed and coupled with dual-signal output system to construct a biomimetic electrochemical ratiometric strategy for ultrasensitive target DNA analysis. The tetrahedral structure provided rigid support for the pedal, ensuring efficient replacement of the rail chain modified with ferrocene. By conjugating cholesterol molecules to one vertex of MTM, it is decorated on a lipid bilayer. This molecular architecture confers lateral movement of MTM on an electrode surface while prevents its detachment from the system. The methylene blue tagged hairpin probe provides constant power to support MTM swim on lipid bilayer. Compared with the conventional motion mode, the lateral moving mechanism has the fastest reaction rate and the highest signal-to-noise ratio. Additionally, the dual-signal reporting system further improves the accuracy of target detection on the basis of ensuring motion efficiency. The work improved movement efficiency and shortened time fragment. A linear relationship between the ratio value of two reporters and target DNA concentration was observed from 0.5 fM to 50 pM with a detection limit of 28 aM. The lateral motion mode of DNA machine coalescing with ratiometric system made this sensing platform ultrasensitive and accurate, which holds new avenue of early diagnosis.

RNF168 suppresses the cancer stem cell-like traits of nonsmall cell lung cancer cells by mediating RhoC ubiquitination.

The critical roles of E3 ubiquitin ligase RNF168 have been widely revealed in various tumors, however, its roles in lung cancer progression are still confusing. Here, we found that RNF168 expression is positively correlated with the overall survival, first-progression survival, and postprogression survival of lung adenocarcinoma, but not correlated with these survivals of squamous cell carcinoma of lung. Furthermore, it was shown that RNF168 mRNA expression is lowly expressed in lung adenocarcinoma tissues, but highly expressed in squamous cell carcinoma of lung. Functional experiments indicated that RNF168 overexpression significantly suppressed the cancer stem cell (CSC)-like traits of nonsmall cell lung cancer (NSCLC) cells, as characterized by the attenuation of sphere-formation ability, ALDH activity, and the expression of lung CSC markers. Mechanistic studies demonstrated that RNF168 facilitated the ubiquitination of RhoC, which had been considered as a fascinating target for CSCs, and thus promoted RhoC protein degradation. Notably, RNF168 failed to affect the mRNA expression of RhoC and overexpression of RhoC rescued the inhibitory effects of RNF168 overexpression on the CSC-like traits of NSCLC cells. Therefore, this study revealed RNF168 as a novel regulator of RhoC protein in NSCLC cells, this RNF168/RhoC regulatory axis might be a potential target for NSCLC treatment.

Covalent Immobilization of Cellulase onto Amino and Graphene Oxide Functionalized Magnetic Fe2O3/Fe3O4@SiO2 Nanocomposites.

Magnetic Fe2O3/Fe3O4@SiO2 nanocomposites were prepared via the citric-alcohol solution combustion process. The obtained nanocomposites were characterized with SEM, XRD, VSM, TEM, EDS, HRTEM, and FTIR techniques. The results revealed that the magnetic Fe2O3/Fe3O4@SiO2 nanocomposites were successfully obtained with the average grain size of 87 nm and the saturation magnetization of 36 emu/g. After the surface of magnetic Fe2O3/Fe3O4@SiO2 nanocomposites was functionalized by amino group, the amino-functionalized Fe2O3/Fe3O4@SiO2-NH2 nanocomposites were loaded onto graphene oxide based on Mitsunobu reaction. Subsequently, the cellulase was immobilized onto Fe2O3/Fe3O4@SiO2-NH-GO nanocomposites by a glutaraldehyde-mediated Schiff base reaction. The immobilization conditions were optimized by adjusting the pH, temperature, and cellulase dose. The results revealed that optimized immobilization conditions were determined to be temperature of 50 °C, pH of 5, and cellulase solution of 0.1 mL. 97.3% cellulase were successfully immobilized under the optimal conditions. The catalytic performances of the immobilized cellulase were also evaluated. The maximum activity was achieved at pH 4, and 50 °C with cellulase solution of 0.4 mL.

Delivery of apigenin-loaded magnetic Fe2O3/Fe3O4@mSiO2 nanocomposites to A549 cells and their antitumor mechanism.

This study introduces a mesoporous magnetic nano-system for the delivery of apigenin (API). A targeted therapeutic drug delivery system was prepared based on Fe2O3/Fe3O4@mSiO2-HA nanocomposites. Magnetic Fe2O3/Fe3O4 heterogeneous nanoparticles were first prepared via the rapid-combustion process. The effects of solvent type, solvent volume, calcination temperature, and calcination time on the crystal size and magnetism of the Fe2O3/Fe3O4 heterogeneous nanoparticles were investigated. The mesoporous silica shell was deposited on the Fe2O3/Fe3O4 heterogeneous nanoparticles using an improved Stöber method. HA was exploited as the targeting ligand. The specific surface area of the Fe2O3/Fe3O4@mSiO2 nanocomposites was 369.6 m2/g, which is 19 times higher than that of the magnetic Fe2O3/Fe3O4 heterogeneous nanoparticle cores. Drug release properties from the Fe2O3/Fe3O4@mSiO2-HA nanocomposites were studied, and the result showed that API-loaded nano-system had sustained release effect. Prussian blue staining and electrochemical performance variation showed that an external magnetic field facilitated cell uptake of Fe2O3/Fe3O4@mSiO2-HA nanocomposites. MTT assays showed that the cell inhibition effect of API-Fe2O3/Fe3O4@mSiO2-HA was stronger than that of free API at the same drug dose under a magnetic field and Fe2O3/Fe3O4@mSiO2-HA nanocomposites showed good biocompatibility. Fluorescence imaging, flow cytometry, western blot, reactive oxygen species (ROS), Superoxide dismutase (SOD) and malondialdehyde (MDA) kits verified that the enhanced therapeutic action was due to the promotion of apoptosis, lipid peroxidation, and ferroptosis. The magnetic nano-system (Fe2O3/Fe3O4@mSiO2-HA) showed good magnetic targeting and active hyaluronic acid targeting, and has the potential to provide a targeted delivery platform for many antitumor drugs.

The correlation of microRNA-499 rs3746444 T>C locus with the susceptibility of gastric cancer: from a case-control study to a meta-analysis.

The relationship between rs3746444 T>C single-nucleotide polymorphism (SNP) in microRNA (mir)-499 and risk of gastric cancer (GC) has been widely investigated. However, the association was still unconfirmed. Here, we first recruited 490 GC patients and 1476 controls, and conducted a case-control study. And we did not find any association between rs3746444 T>C SNP polymorphism and risk of GC. Subsequently, we conducted a meta-analysis to explore the association of mir-499 rs3746444 polymorphism with GC development. Two authors searched the PubMed and EMBASE databases up to October 15, 2019 independently. Finally, nine literatures involving 12 independent studies were included. In total, 3954 GC cases and 9745 controls were recruited for meta-analysis. The results suggested that allele model, homozygote model and recessive model could increase the risk of overall GC (P = 0.002, 0.009 and 0.013, respectively). When we excluded the studies violated HWE, this association was also found in allele model (P = 0.020) and dominant model (P= 0.044). In subgroup analyses, we identified that rs3746444 SNP in mir-499 increased the risk of GC in Asians and gastric cardiac adenocarcinoma (GCA) subgroups. No significant bias of selection was found (all P>0.1). Test of sensitivity analysis indicated that our findings were stable. Additionally, we found that the power value was 0.891 in the allele model, suggesting the reliability of our findings. In summary, our analysis confirmed the association between rs3746444 and the risk of GC, especially in Asians and in patients with GCA.

Investigation of leptin receptor rs1137101 G>A polymorphism with cancer risk: evidence from 35936 subjects.

Leptin receptor (LEPR) signaling may be involved in promoting angiogenesis and proliferation, inhibiting apoptosis and playing a vital role in the progression of carcinogenesis. A number of studies have focused on the association of LEPR rs1137101 variants with susceptibility of cancer, however, the observed results were controversial. We searched literature on the relationship of LEPR rs1137101 G>A polymorphism with cancer risk by using PubMed and Embase databases, covering all publications up to 14 October 2018. In total, 44 case-control studies with 35,936 subjects were included. After combining all eligible studies, we identified null relationship between LEPR gene rs1137101 G>A polymorphism and overall cancer risk [A vs. G: odds ratio (OR ) =  0.97, 95% confidence interval (CI ) =  0.89-1.06, P = 0.547; AA vs. GG: OR  =  0.93, 95% CI  =  0.78-1.13, P = 0.476; AA/GA vs. GG: OR  =  0.99, 95% CI  =  0.91-1.09, P= 0.890 and AA vs. GA/GG: OR  = 0.92, 95% CI  =  0.82-1.04, P= 0.198]. However, in a subgroup analysis, there was an increased susceptibility of oral and oropharyngeal cancer in AA vs. GA/GG genetic model (OR, 1.83; 95% CI, 1.01-3.33; P=0.048). Considering the limited participants were included, the findings might be underpowered. Sensitivity analysis identified that any independent study omitted did not materially influence the pooled ORs and CIs. The results of publication bias detection showed that there was no evidence of bias. In summary, this analysis indicates that no significant association of cancer risk was identified to be correlated with rs1137101 G>A variants, even in stratified analyses.

Decoy receptor 3 polymorphisms are not associated with the risk of esophageal cancer in a Chinese population.

Esophageal cancer (EC) is the sixth most common cancer worldwide, and esophageal squamous-cell carcinoma (ESCC) accounts for more than 90% of ECs. We hypothesized that genetic factors might play an important role in ESCC carcinogenesis. We conducted a hospital-based case-control study to evaluate the association between two single nucleotide polymorphisms of decoy receptor 3 (DcR3), namely, rs2297441 G > A and rs2257440 T > C, on the ESCC risk. In all, 629 ESCC cases and 686 controls were included. Genotypes were determined using the ligation detection reaction method. When the DcR3 rs2297441 GG homozygote genotype was used as the reference group, the GA genotype showed no association with the ESCC risk (GA versus GG: adjusted OR = 1.11, 95% CI = 0.88-1.40, p = 0.396); similarly, even the TT genotype showed no association with the ESCC risk (AA versus GG: adjusted OR = 0.80, 95% CI = 0.55-1.18, p = 0.268). Logistic regression analyses revealed that the DcR3 rs2257440 T > C polymorphism was not associated with the ESCC risk. DcR3 rs2297441 G > A and DcR3 rs2257440 T > C polymorphisms may not contribute to the ESCC risk, and additional, larger studies are required to confirm our results.