Recently, long noncoding RNAs (lncRNAs) have been identified as critical regulators in numerous types of cancers, including non-small cell lung cancer (NSCLC). X inactivate-specific transcript (XIST) ...has been found to be up-regulated and acts as an oncogene in gastric cancer and hepatocellular carcinoma, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Here, we identified XIST as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found that XIST is over-expressed in NSCLC, and its increased level is associated with shorter survival and poorer prognosis. Knockdown of XIST impaired NSCLC cells proliferation, migration and invasion in vitro, and repressed the tumorigenicity of NSCLC cells in vivo. Mechanistically, RNA immune-precipitation (RIP) and RNA pull-down experiment demonstrated that XIST could simultaneously interact with EZH2 to suppress transcription of its potential target KLF2. Additionally, rescue experiments revealed that XIST's oncogenic functions were partly depending on silencing KLF2 expression. Collectively, our findings expound how XIST over-expression endows an oncogenic function in NSCLC.
•XIST is up-regulated in human primary NSCLC tissues and cell lines.•Knockdown of XIST represses NSCLC cell proliferation, migration and invasion, in vitro and vivo.•XIST represses KLF2 expression via directly binding with EZH2 in NSCLC cells.•XIST's oncogenic functions are partially through directly binding with EZH2, and then epigenetically repressing KLF2 expression.
Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma ...membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.
Two natural biomass derivatives i.e., tannic acid (TA) and phosphorylated-cellulose nanofibrils (P-CNFs) were employed to decorate graphene oxide network and the as-prepared flame-retardant GTP paper ...with ultrasensitive fire alarm response can be applied as desirable smart fire alarm sensor material.
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•Biomass-derivatives decorated graphene oxide networks were fabricated via a facile strategy.•The synergistic reinforcing effect was formed in the hybrid networks based on bionic design.•The bio-based hybrid networks showed excellent flame resistance and structural stability.•Ultrasensitive fire alarm time of < 1 s and desirable fire early warning responses were achieved.•Such hybrid networks can be used as sustainable fireproof and fire alarm sensor materials.
Effective utilization of natural biomass-derivatives for developing sustainable, mechanically robust, and fireproof materials remains a huge challenge in fire safety and prevention field. Herein, based on bionic design, the hybrid interconnected networks composed of two-dimensional (2D) graphene oxide (GO) nanosheets, renewable one-dimensional (1D) phosphorylated-cellulose nanofibrils (P-CNFs) and tannic acid molecules (TA) were prepared via a green and facile evaporation-induced self-assembly strategy. Through construction of the multiple synergistic interactions among the TA, P-CNFs and GO, the optimized 1D/2D interconnected networks with hierarchical nacre-like structure were achieved and exhibited improved mechanical properties (tensile strength and Young’s modulus up to ∼ 132 MPa and ∼ 7 GPa, i.e. ∼ 3.6 and ∼ 14 times higher than that of the pure GO paper), good structural stability in various environments (aqueous solutions with different pH values), excellent flame retardancy (keeping structural integrity after flame attack), and ultrasensitive fire alarm functions (e.g., ultrafast flame alarm time of < 1 s and sensitive fire warning responses). Further, such 1D/2D interconnected networks can act as effective flame-retardant nanocoatings to significantly improve the flame retardancy of combustible PU foam materials (e.g., ∼48% decrease in peak heat release rate at only 10 wt% content). Based on the structure observation and analysis, the related synergistic reinforcing and flame-retardant mechanisms were proposed and clarified. Clearly, this work provides a new route for design and development of environmentally friendly fireproof and fire alarm materials based on utilization of natural biomass-derivatives.
Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung ...cancer (NSCLC) still remain mainly undetermined.
qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2.
LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8
T cell population in LA-4/SLN-205-derived tumors through targeting TGF-β. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83-123 nucleotide nt) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612-727 amino acid aa) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel-Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells.
In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.
A graphene oxide (GO)-based smart fire alarm sensor (FAS) has gained rapidly increasing research interest in fire safety fields recently. However, it still remains a huge challenge to obtain ...desirable GO-based FAS materials with integrated performances of mechanical flexibility/robustness, harsh environment-tolerance, high-temperature resistance, and reliable fire warning and protection. In this work, based on bionic design, the supermolecule melamine diborate (M·2B) was combined with GO nanosheets to form supramolecular cross-linking nanosystems, and the corresponding GO-M·2B (GO/MB) hybrid papers with a nacre-like micro/nano structure were successfully fabricated via a gel-dry method. The optimized GO/MB paper exhibits enhanced mechanical properties, e.g., tensile strength and toughness up to ∼122 MPa and ∼1.72 MJ/m3, respectively, which is ∼3.5 and ∼6.6 times higher than those of the GO paper. Besides, it also shows excellent structural stability even under acid/alkaline solution immersion and water bath ultrasonication conditions. Furthermore, due to the presence of promoting reduction effect and atom doping reactions in GO network, the resulting GO/MB network displays exceptional high-temperature resistance, sensitive fire alarm response (∼0.72 s), and ultralong alarming time (>1200 s), showing promising fire safety and protection application prospects as desirable FAS and fire shielding material with excellent comprehensive performances. Therefore, this work provides inspiration for the design and fabrication of high-performance GO-based smart materials that combine fire shielding and alarm functions.
Highlights
Graphene oxide-based hybrid networks were fabricated via introducing multi-amino molecule with triple roles (i.e., cross-linker, fire retardant and reducing agent).
The optimized hybrid ...network with mechanically robust, exceptional intumescent effect and ultra-sensitive fire alarm response (~ 0.6 s) can be used as desirable smart fire alarm sensor materials.
Exceptional fire shielding performances, e.g., ~ 60% reduction in peak heat release rate and limiting oxygen index of ~ 36.5%, are achieved, when coated such hybrid network onto combustible polymer foam.
Smart fire alarm sensor (FAS) materials with mechanically robust, excellent flame retardancy as well as ultra-sensitive temperature-responsive capability are highly attractive platforms for fire safety application. However, most reported FAS materials can hardly provide sensitive, continuous and reliable alarm signal output due to their undesirable temperature-responsive, flame-resistant and mechanical performances. To overcome these hurdles, herein, we utilize the multi-amino molecule, named HCPA, that can serve as triple-roles including cross-linker, fire retardant and reducing agent for decorating graphene oxide (GO) sheets and obtaining the GO/HCPA hybrid networks. Benefiting from the formation of multi-interactions in hybrid network, the optimized GO/HCPA network exhibits significant increment in mechanical strength, e.g., tensile strength and toughness increase of ~ 2.3 and ~ 5.7 times, respectively, compared to the control one. More importantly, based on P and N doping and promoting thermal reduction effect on GO network, the excellent flame retardancy (withstanding ~ 1200 °C flame attack), ultra-fast fire alarm response time (~ 0.6 s) and ultra-long alarming period (> 600 s) are obtained, representing the best comprehensive performance of GO-based FAS counterparts. Furthermore, based on GO/HCPA network, the fireproof coating is constructed and applied in polymer foam and exhibited exceptional fire shielding performance. This work provides a new idea for designing and fabricating desirable FAS materials and fireproof coatings.
Background
Lung cancer is still one of the most serious causes of cancer‐related deaths all over the world. MicroRNAs (miRNAs) are defined as small non‐coding RNAs which could play a pivotal role in ...post‐transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC.
Aims
To emphasize a variety of tissue‐specific miRNAs, circulating miRNAs and miRNA‐derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients.
Materials & Methods
In the current review, we paid attention to the significant discoveries of preclinical and clinical studies, which performed on tissue‐specific miRNA, circulating miRNA and exosomal miRNA. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase.
Results
A variety of tissue‐specific miRNAs and circulating miRNAs with high sensitivity and specificity which could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In addition, we emphasize that the miRNA‐derived exosomes become novel diagnostic biomarkers potentially in these patients with NSCLC.
Conclusion
MiRNAs have emerged as non‐coding RNAs, which have potential to be candidates for the diagnosis and therapy of NSCLC.
E2F transcription factors (E2Fs), a group of genes that encode a family of transcription factors, have been identified as being involved in the tumor progression of various cancer types. Increasing ...experimental evidence indicates that E2Fs are implicated in breast cancer tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be analyzed. Herein we investigated the transcriptional and survival data of E2Fs in patients with breast cancer from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1-3 and 5-8 were higher in breast cancer tissues than in normal breast tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2, 5, 7, and 8 were correlated with advanced tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that the high transcription levels of E2F1-3, 5, 7, and 8 were associated with low relapse-free survival in all of the patients with breast cancer. Conversely, high E2F4 and E2F6 levels predicted high relapse-free survival in these patients. This study implied that E2F1-3, 5, 7, and 8 are potential targets of precision therapy for patients with breast cancer and that E2F4 and 6 are new biomarkers for the prognosis of breast cancer.
A multicomponent metallic glass (MG) with highly efficient and anomalous durability for catalyzing water splitting is reported. The outstanding performance of the MG catalyst contributed by ...self‐optimized active sites originates from the intrinsic chemical heterogeneity and selective dealloying on the disordered surface; thus, a new mechanism for improving the durability of catalysts is uncovered.
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