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Lung adenocarcinoma (LUAD) accounts for almost 40% of lung cancers, leading to significant associated morbidity and mortality rates. However, the mechanism of LUAD tumorigenesis remains far from clear. Here, we scanned downregulated genes involved in LUAD sourced from Cancer Genome Atlas and Gene Expression Omnibus data and focused on G protein-coupled receptor 133 (GPR133). We offer compelling evidence that GPR133 was expressed at low levels in the setting of LUAD and higher expression was positively related with a better prognosis among LUAD patients. Functionally, GPR133 inhibited cell proliferation and tumor growth in vitro and in vivo. Regarding the mechanism, flow cytometry assays and western blot assays showed that GPR133 enhanced p21 and decreased cyclin B1 expression, thus triggered LUAD cells at G2/M-phase arrest. Consistent with this, we evaluated the expression levels of cell-cycle biomarkers and found that Bioinformatics analysis combined with N6 -methyladenosine (m6 A; methylation at the N6 position in adenosine) RNA immunoprecipitation-qPCR (MeRIP-qPCR) assay indicated that GPR133 expression was downregulated by this modification. Moreover, we observed that methyltransferase-like 3 was impaired in LUAD and that it is able to significantly increase levels of GPR133 by enhancing its RNA stability. In conclusion, we found that GPR133 expression was downregulated in LUAD via m6 A modification. Increasing GPR133 levels could suppress LUAD cell proliferation and tumor growth.

Long non-coding RNAs (lncRNAs) have been potentially identified as new diagnostic markers, prognostic factors and therapeutic targets in cancer. The acquisition of a mesenchymal (MES) phenotype in glioblastomas (GBMs) results into therapeutic resistance and poor clinical outcomes. The correlation between lncRNAs and MES differentiation remains elusive. Here, we report that LINC01057 as a lncRNA is overexpressed in GBMs, especially in MES subtype. LINC01057 knockdown suppresses proliferation, invasion and radioresistance of GBM cells in vitro, and tumor growth in vivo. LINC01057 knockdown leads to loss of MES signature in MES subpopulation of GBM cells, but LINC01057 overexpression promotes MES differentiation in proneural (PN) subpopulation. LINC01057 interacts with IKKα and maintains IKKα nucleus localization, leading to effective chromatin accessibility at NF-κB responsive promoters via histone modification and final NF-κB activation. IKKα knockdown disrupts the effect of LINC01057 overexpression on PN to MES transition (PMT). LINC01057 level is negatively correlated with patient prognosis in MES-subtype GBM. Collectively, our findings uncover LINC01057 as a regulator of NF-κB signaling to promote MES differentiation and a potential target for therapeutic intervention for MES-subtype GBM.

Glioma is the most common primary brain tumor with poor prognosis and high mortality. The purpose of this study was to use the epigenetic signature to predict prognosis and evaluate the degree of immune infiltration in gliomas. We integrated gene expression profiles and DNA methylation data of lower-grade glioma and glioblastoma to explore epigenetic differences and associated differences in biological function. Cox regression and lasso analysis were used to develop an epigenetic signature based on eight DNA methylation sites to predict prognosis of glioma patients. Kaplan–Meier analysis showed that the overall survival time of high- and low-risk groups was significantly separated, and ROC analysis verified that the model had great predictive ability. In addition, we constructed a nomogram based on age, sex, 1p/19q status, glioma type, and risk score. The epigenetic signature was obviously associated with tumor purity, immune checkpoints, and tumor-immune infiltrating cells (CD8+ T cells, gamma delta T cells, M0 macrophages, M1 macrophages, M2 macrophages, activated NK cells, monocytes, and activated mast cells) and thus, it may find application as a guide for the evaluation of immune infiltration or in treatment decisions in immunotherapy.

Lung adenocarcinoma (LUAD) accounts for almost 40% of lung cancers, leading to significant associated morbidity and mortality rates. However, the mechanism of LUAD tumorigenesis remains far from clear. Here, we scanned down-regulated genes involved in LUAD sourced from The Cancer Genome Atlas and Gene Expression Omnibus data and focused on G protein-coupled receptor 133 (GPR133). We offer compelling evidence that GPR133 was expressed at low levels in the setting of LUAD, and higher expression was positively related to a better prognosis among patients with LUAD. Functionally, GPR133 inhibited cell proliferation and tumor growth in vitro and in vivo. Regarding the mechanism, flow cytometry assays and western blot assays showed that GPR133 enhanced p21 and decreased cyclin B1 expression, thus triggering LUAD cells at G2/M-phase arrest. Consistent with this, we evaluated the expression levels of cell-cycle biomarkers and found that bioinformatics analysis combined with N

Background Lung squamous cell carcinoma (LUSC), as the second frequent subtype of lung cancer, causes lots of mortalities primarily due to a lack of precise prognostic markers and timely treatment intervention. Previous studies have constructed several risk prognostic models based on DNA methylation sites in multiple tumors, whereas, DNA methylation signature of LUSC remains to be built, and its predictive value need to be evaluated. Methods The genome-wide DNA methylation data of LUSC samples was obtained from The Cancer Genome Atlas dataset. Univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) were implemented to identify DNA methylation sites related to overall survival of LUSC patients. Thus, we performed multivariate Cox regression to establish a DNA methylation signature. The Kaplan-Meier (K-M) survival curves and time-dependent receiver operating characteristic (ROC) curves were plotted to estimate the prognostic power of the signature. Comparison with other known prognostic biomarkers, our DNA methylation signature showed higher predictive specificity and sensitivity. In addition, multivariate Cox regression screened out independent prognostic factors and constructed a nomogram. Results Several statistical methods were performed to construct an 11-DNA methylation signature. LUSC patients were divided into low- and high-risk group based on risk score, and high-risk group had a shorter survival time. According to the results of K-M and ROC analyses, the 11-DNA methylation signature showed significant sensitivity and specificity in predicting the LUSC patients' overall survival. Finally, we integrated some independent prognostic factors (risk score, metastasis stage, and tobacco smoking history) to construct a nomogram, which has excellent prognostic power and may provide guidance for the therapeutic strategies. Conclusions We constructed the first risk prognosis model based on DNA methylation site in LUSC, which showed better predictive ability. In addition, a nomogram integrating the DNA methylation signature, metastasis stage, and tobacco smoking history was developed.

Flag leaf-related traits (FLRTs) are determinant traits affecting plant architecture and yield potential in wheat (Triticum aestivum L.). In this study, three related recombinant inbred line (RIL) populations with a common female parent were developed to identify quantitative trait loci (QTL) for flag leaf width (FLW), length (FLL), and area (FLA) in four environments. A total of 31 QTL were detected in four environments. Two QTL for FLL on chromosomes 3B and 4A (QFll-3B and QFll-4A) and one for FLW on chromosome 2A (QFlw-2A) were major stable QTL. Ten QTL clusters (C1–C10) simultaneously controlling FLRTs and yield-related traits (YRTs) were identified. To investigate the genetic relationship between FLRTs and YRTs, correlation analysis was conducted. FLRTs were found to be positively correlated with YRTs especially with kernel weight per spike and kernel number per spike in all the three RIL populations and negatively correlated with spike number per plant. Appropriate flag leaf size could benefit the formation of high yield potential. This study laid a genetic foundation for improving yield potential in wheat molecular breeding programs.

Due to the interfacial reflection on the surface of the optoelectronic material and the device, the conversion efficiency to solar energy is limited. Here, a simple method of fabricating bio-inspired TiO2 micro-pyramids with polypyrrole (PPy) nanoparticles on both sides of glass was introduced. This bio-inspired structure, retarding the change of the refractive index from air to sample surface, was fabricated by soft lithography and self-assembly. The two-sided bio-inspired coating presents excellent antireflective performance and photocatalytic activity.