CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer.

BACKGROUND: Bladder cancer (BCa) is the fourth most common malignant tumor with a poor prognosis worldwide. Further exploration and research are needed to unmask the underlying roles and molecular mechanisms of circular RNAs. In the current study, our findings showed that circXRN2 suppresses tumor progression driven by histone lactylation by activating the Hippo pathway in human bladder cancer. METHODS: RNA immunoprecipitation (RIP) followed by circRNA sequencing confirmed circXRN2 as the research object. Overexpression of circXRN2 and knockdown of TAZ/YAP further verified the biological functions in T24 and TCCSUP cells. RIP, immunoprecipitation and coimmunoprecipitation were used to elucidate the interaction between circXRN2 and LATS1. A Seahorse metabolic analyzer was used to determine the glycolytic rate. Cleavage under targets and Tagmentation (CUT&Tag) and chromatin immunoprecipitation (ChIP) were employed to ensure the regulatory roles of H3K18 lactylation in the transcriptional activity of LCN2. RESULTS: CircXRN2 is aberrantly downregulated in bladder cancer tissues and cell lines. CircXRN2 inhibits the proliferation and migration of tumor cells both in vitro and in vivo. In addition, circXRN2 serves as a negative regulator of glycolysis and lactate production. Mechanistically, circXRN2 prevents LATS1 from SPOP-mediated degradation by binding to the SPOP degron and then activates the Hippo signaling pathway to exert various biological functions. The circXRN2-Hippo pathway regulatory axis further modulates tumor progression by inhibiting H3K18 lactylation and LCN2 expression in human bladder cancer. CONCLUSIONS: CircXRN2 suppresses tumor progression driven by H3K18 lactylation by activating the Hippo signaling pathway in human bladder cancer. Our results indicated novel therapeutic targets and provided promising strategies for clinical intervention in human bladder cancer.

Quality Assessment and Ripeness Prediction of Table Grapes Using Visible-Near-Infrared Spectroscopy.

Ripeness significantly affects the commercial values and sales of fruits. In order to monitor the change of grapes' quality parameters during ripening, a rapid and nondestructive method of visible-near-infrared spectral (Vis-NIR) technology was utilized in this study. Firstly, the physicochemical properties of grapes at four different ripening stages were explored. Data evidenced increasing color in redness/greenness (a*) and Chroma (C*) and soluble solids (SSC) content and decreasing values in color of lightness (L*), yellowness/blueness (b*) and Hue angle (h*), hardness, and total acid (TA) content as ripening advanced. Based on these results, spectral prediction models for SSC and TA in grapes were established. Effective wavelengths were selected by the competitive adaptive weighting algorithm (CARS), and six common preprocessing methods were applied to pretreat the spectra data. Partial least squares regression (PLSR) was applied to establish models on the basis of effective wavelengths and full spectra. The predictive PLSR models built with full spectra data and 1st derivative preprocessing provided the best values of performance parameters for both SSC and TA. For SSC, the model showed the coefficients of determination for calibration (RCal2) and prediction (RPre2) set of 0.97 and 0.93, respectively, the root mean square error for calibration set (RMSEC) and prediction set (RMSEP) of 0.62 and 1.27, respectively; and the RPD equal to 4.09. As for TA, the optimum values of RCal2, RPre2, RMSEC, RMSEP and RPD were 0.97, 0.94, 0.88, 1.96 and 4.55, respectively. The results indicated that Vis-NIR spectroscopy is an effective tool for the rapid and non-destructive detection of SSC and TA in grapes.

Discrimination of Maturity Stages of Cabernet Sauvignon Wine Grapes Using Visible-Near-Infrared Spectroscopy.

Grape quality and ripeness play a crucial role in producing exceptional wines with high-value characteristics, which requires an effective assessment of grape ripeness. The primary purpose of this research is to explore the possible application of visible-near-infrared spectral (Vis-NIR) technology for classifying the maturity stages of wine grapes based on quality indicators. The reflection spectra of Cabernet Sauvignon grapes were recorded using a spectrometer in the spectral range of 400 nm to 1029 nm. After measuring the soluble solids content (SSC), total acids (TA), total phenols (TP), and tannins (TN), the grape samples were categorized into five maturity stages using a spectral clustering method. A traditional supervised classification method, a support vector machine (SVM), and two deep learning techniques, namely stacked autoencoders (SAE) and one-dimensional convolutional neural networks (1D-CNN), were employed to construct a discriminant model and investigate the association linking grape maturity stages and the spectral responses. The spectral data went through three commonly used preprocessing methods, and feature wavelengths were extracted using a competitive adaptive reweighting algorithm (CARS). The spectral data model preprocessed via multiplicative scattering correction (MSC) outperformed the other two preprocessing methods. After preprocessing, a comparison was made between the discriminant models established with full and effective spectral data. It was observed that the SAE model, utilizing the feature spectrum, demonstrated superior overall performance. The classification accuracies of the calibration and prediction sets were 100% and 94%, respectively. This study showcased the dependability of combining Vis-NIR spectroscopy with deep learning methods for rapidly and accurately distinguishing the ripeness stage of grapes. It has significant implications for future applications in wine production and the development of optoelectronic instruments tailored to the specific needs of the winemaking industry.

Circular RNA-regulated autophagy is involved in cancer progression.

Circular RNAs (circRNAs) are a sort of long, non-coding RNA molecules with a covalently closed continuous ring structure without 5'-3' polarity and poly-A tail. The modulative role of circRNAs in malignant diseases has been elucidated by many studies in recent years via bioinformatics and high-throughput sequencing technologies. Generally, circRNA affects the proliferative, invasive, and migrative capacity of malignant cells via various mechanisms, exhibiting great potential as novel biomarkers in the diagnoses or treatments of malignancies. Meanwhile, autophagy preserves cellular homeostasis, serving as a vital molecular process in tumor progression. Mounting studies have demonstrated that autophagy can not only contribute to cancer cell survival but can also induce autophagic cell death in specific conditions. A growing number of research studies have indicated that there existed abundant associations between circRNAs and autophagy. Herein, we systemically reviewed and discussed recent studies on this topic in different malignancies and concluded that the circRNA-autophagy axis played crucial roles in the proliferation, metastasis, invasion, and drug or radiation resistance of different tumor cells.

HO-1 Protects Remnant Liver against Dysfunction after Major Hepatectomy in Humans.

OBJECTIVE: During major resection of liver carcinoma, liver regeneration (LR) is induced by various clinical and biological factors. Heme oxygenase (HO)-1 has been found as a key inducer of LR in preclinical trial. The clinical evidence for the role of HO-1 in liver dysfunction (LD) including LR is still unknown and has been included in this study. METHODS: Therefore, plasma HO-1 were monitored during perioperative period in 65 patients with hepatectomy, with 35 training and 30 validation cohorts. LD were evaluated by liver function serum markers and calculation of regeneration indices, respectively. RESULTS: In the training setting, HO-1 levels were remarkably reduced after liver resection (P < 0.001) and gradually recovered within 7 days after surgery. Preoperative HO-1 specifically predicted LD during the first week after surgery (AUC: 0.757; P = 0.01). In patients with LD and complications after surgery, HO-1 levels decreased throughout the perioperative period. In addition, we had also confirmed that low levels of HO-1 (<169 ng/ml) before surgery were associated with an increase in the incidence of postoperative LD and morbidity (P = 0.007, P = 0.045), and decrease of liver regeneration (P = 0.005). And HO-1 was an independent predictor for poor clinical outcome. CONCLUSIONS: We had provided the first clinical data verifying that human HO-1 was related to LD. Consequently, HO-1 levels can be used as effective clinical indicators to predict LD and clinical outcome, and can be used as intervention target before liver resection.

A Novel Assessment Model Based on Molecular Subtypes of Hypoxia-Related LncRNAs for Prognosis of Bladder Cancer.

Hypoxia is a common feature in various tumors that regulates aggressiveness. Previous studies have demonstrated that some dysregulated long non-coding RNAs (lncRNAs) are correlated with tumor progression, including bladder cancer (BCa). However, the prognostic effect of hypoxia-related lncRNAs (HRLs) and their clinical relevance, as well as their regulatory effect on the tumor immune microenvironment, are largely unknown in BCa. A co-expression analysis between hypoxia genes and lncRNA expression, which was downloaded from the TCGA database, was performed to identify HRLs. Univariate Cox regression analysis was performed to select the most desirable lncRNAs for molecular subtype, and further LASSO analysis was performed to develop a prognostic model. This molecular subtype based on four HRLs (AC104653, AL136084, AL139393, and LINC00892) showed good performance in the tumor microenvironment and tumor mutation burden. The prognostic risk model suggested better performance in predicting BCa patients' prognosis and obtained a close correlation with clinicopathologic features. Furthermore, four of five first-line clinical chemotherapies showed different sensitivities to this model, and nine immune checkpoints showed different expression in the molecular subtypes or the risk model. In conclusion, this study indicates that this molecular subtype and risk model based on HRLs may be useful in improving the prognostic prediction of BCa patients with different clinical situations and may help to find a useful target for tumor therapy.

Comprehensive analysis of pyroptosis regulators and tumor immune microenvironment in clear cell renal cell carcinoma.

BACKGROUND: Increasing evidence has indicated that pyroptosis could regulate the tumor immune microenvironment (TIME) to affect the tumor development. As a highly immunogenic tumor, clear cell renal cell carcinoma (ccRCC) can benefit from immunotherapy, but related research on pyroptosis in the TIME of ccRCC is still deficient. METHODS: Available data derived from TCGA and GEO databases were analyzed to identify the different expression profiles of pyroptosis in ccRCC and normal tissues, and the correlation of pyroptosis regulators with TIME was evaluated in ccRCC. RESULTS: According to consensus clustering analysis, two differential expression levels of subtypes were identified to affect patient prognosis, and were related to histological tumor stage and grade. Immune cells were calculated by the CIBERSORT algorithm. Higher infiltrated levels of B cells naive, T cells CD4 memory resting, NK cells resting, monocytes, macrophages were observed in Cluster 1, while higher infiltrated levels of CD8+ T cells, T follicular helper cells, and Tregs were observed in Cluster 2. Gene set enrichment analysis indicated that Cluster 2 was enriched in multiple immune-related pathways, including the JAK-STAT signaling pathway. Moreover, overexpression of eight immune checkpoints was related to ccRCC development, especially in Cluster 2. As four potentially key pyroptosis regulators, AIM2, CASP5, NOD2, and GZMB were confirmed to be upregulated in ccRCC by RT-qPCR analysis and further verified by the HPA database. Further pan-cancer analysis suggested that these four pyroptosis regulators were differentially expressed and related to the TIME in multiple cancers. CONCLUSION: The present study provided a comprehensive view of pyroptosis regulators in the TIME of ccRCC, which may provide potential value for immunotherapy.

Circular RNA CircPPP1CB Suppresses Tumorigenesis by Interacting With the MiR-1307-3p/SMG1 Axis in Human Bladder Cancer.

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA (ncRNA), which is characterized with a closed circular structure. A growing body of evidence has verified the vital roles of circRNAs in human cancer. In this research, we selected circPPP1CB as a study object by circRNA sequencing and quantitative real-time PCR (qRT-PCR) validation in human bladder cancer (BC). CircPPP1CB is downregulated in BC and is negatively correlated with clinical stages and histological grades. Functionally, circPPP1CB modulated cell growth, metastasis, and epithelial-to-mesenchymal transition (EMT) process in vitro and in vivo. Mechanically, we performed various experiments to verify the circPPP1CB/miR-1307-3p/SMG1 regulatory axis. Taken together, our results demonstrated that circPPP1CB participates in tumor growth, metastasis, and EMT process by interacting with the miR-1307-3p/SMG1 axis, and that circPPP1CB might be a novel therapeutic target and diagnostic biomarker in human BC.

Thymoquinone Suppresses the Proliferation, Migration and Invasiveness through Regulating ROS, Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells.

Bladder carcinoma is among the top 10 most frequently diagnosed cancer types in the world. As a phytochemical active metabolic, thymoquinone (TQ) is extracted from seeds of Nigella sativa, possessing various biological properties in a wide range of diseases. Moreover, the outstanding anti-cancer effect of TQ is attracting increasing attentions. In certain circumstances, moderate autophagy is regarded to facilitate the adaptation of malignant cells to different stressors. Conversely, closely linked with the mitochondrial membrane potential (MMP) loss, the upregulation of intracellular reactive oxygen species (ROS) is reported to activate the cell apoptosis in many cancer types. Furthermore, the vital effects of microRNAs in the pathological processes of cancer cells have also been confirmed by previous studies. The present research confirms that TQ restrains the viability, proliferation, migration and invasion through activating caspase-dependent apoptosis in bladder carcinoma cells, which is mediated by TQ induced ROS increase in bladder carcinoma cells. Furthermore, TQ is proved to block the fusion of autophagosomes and lysosomes, causing the accumulation of autophagosomes and subsequent cell apoptosis. In addition, TQ is also found to initiate the miR-877-5p/PD-L1 axis, which suppresses the epithelial mesenchymal transition (EMT) and invasion of bladder carcinoma cells. Taken together, TQ induces the apoptosis through upregulating ROS level and impairing autophagic flux, and inhibiting the EMT and cell invasion via activating the miR-877-5p/PD-L1 axis in bladder carcinoma cells.

Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells.

Betulinic acid (BA), a pentacyclic triterpenoid isolated from tree bark, exhibits antitumor effects against solid malignancies and triggers autophagy and/or apoptosis in human cancer cells. Nonetheless, the relationship between autophagy and apoptosis and the potential modulatory actions of BA on autophagy-dependent bladder cancer cell death remain unclear. The present study showed that BA exposure significantly suppressed viability, proliferation, and migration of EJ and T24 human bladder cancer cells. These effects reflected caspase 3-mediated apoptosis and could be attenuated or abolished by inhibiting ROS production with N-acetyl-L-cysteine, inhibiting autophagy with chloroquine, or silencing ATG7 with targeted siRNA. BA-induced autophagy was evidenced by epifluorescence imaging of lentivirus-induced expression of mCherry-GFP-LC3B and increased expression of two autophagy-related proteins, LC3B-II and TEM. Moreover, enhanced AMPK phosphorylation and decreased mTOR and ULK-1 phosphorylation suggested BA activates autophagy via the AMPK/mTOR/ULK1 pathway. Accordingly, exposure to dorsomorphin (Compound C), an AMPK inhibitor, and AICAR, an AMPK activator, respectively inhibited and stimulated BA-induced autophagy in EJ and T24 cells. The effects of Bmi-1 overexpression in vitro and decreased Bmi-1 expression in BA-treated T24 cell xenografts in nude mice suggested that downregulation of Bmi-1 is the underlying mechanism in BA-mediated, autophagy-dependent apoptosis.

Peroxidase- and UV-triggered oxidase mimetic activities of the UiO-66-NH2/chitosan composite membrane for antibacterial properties.

In this study, UiO-66-NH2 metal-organic framework (MOF) nanoparticles with peroxidase and oxidase mimetic activities were incorporated into a chitosan (CS) matrix by a simple and environmentally friendly method. The UiO-66-NH2/CS composite membrane possesses the peroxidase mimicking activity in the presence of traces of H2O2, thus resulting in good antibacterial properties. Intriguingly, 30 min of UV pre-irradiation of the UiO-66-NH2/CS composite membrane, in the absence of H2O2, still leads to a good antibacterial activity. This was attributed to the oxidase mimetic activity and the peroxidase mimicking activity of UiO-66-NH2. In such a way, the side effects of direct exposure to UV irradiation and H2O2 can be avoided for wound-healing treatments. The antibacterial mechanism was further proved by antibacterial experiments, TMB·2HCl color development experiments, reactive oxygen species generation tests and electron spin resonance tests. As a potential medical antibacterial dressing, in vitro membranes were also investigated.

A positive feedback loop between TAZ and miR-942-3p modulates proliferation, angiogenesis, epithelial-mesenchymal transition process, glycometabolism and ROS homeostasis in human bladder cancer.

BACKGROUND: Transcriptional coactivator with PDZ-binding motif (TAZ) has been reported to be involved in tumor progression, angiogenesis, epithelial-mesenchymal transition (EMT), glycometabolic modulation and reactive oxygen species (ROS) buildup. Herein, the underlying molecular mechanisms of the TAZ-induced biological effects in bladder cancer were discovered. METHODS: qRT-PCR, western blotting and immunohistochemistry were performed to determine the levels of TAZ in bladder cancer cells and tissues. CCK-8, colony formation, tube formation, wound healing and Transwell assays and flow cytometry were used to evaluate the biological functions of TAZ, miR-942-3p and growth arrest-specific 1 (GAS1). QRT-PCR and western blotting were used to determine the expression levels of related genes. Chromatin immunoprecipitation and a dual-luciferase reporter assay were performed to confirm the interaction between TAZ and miR-942. In vivo tumorigenesis and colorimetric glycolytic assays were also conducted. RESULTS: We confirmed the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p expression amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the impacts on cell proliferation, angiogenesis, EMT, glycolysis and ROS levels induced by TAZ knockdown. Furthermore, miR-942-3p restrained the expression of GAS1 to modulate biological behaviors. CONCLUSION: Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression and illustrated that TAZ, miR-942-3p and GAS1 might be potential therapeutic targets for bladder cancer treatment.

Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression.

Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal uroepithelial cells, circRIMS1 was selected as a research object. We further verified by qRT-PCR that circRIMS1 is upregulated in both bladder cancer tissue and cell lines. Proliferation, colony-formation, Transwell migration, invasion, apoptosis, western blotting, and in vivo experiments were utilized to clarify the roles of circRIMS1, microRNA (miR)-433-3p, and cell cycle and apoptosis regulator 1 (CCAR1). For mechanistic investigation, RNA pulldown, fluorescence in situ hybridization (FISH), and luciferase reporter assay confirmed the binding of circRIMS1 with miR-433-3p. Inhibition of circRIMS1 suppressed the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Moreover, the circRIMS1/miR-433-3p/CCAR1 regulatory axis was confirmed to be responsible for the biological functions of circRIMS1. Taken together, our research demonstrated that circRIMS1 promotes tumor growth, migration, and invasion through the miR-433-3p/CCAR1 regulatory axis, representing a potential therapeutic target and biomarker in bladder cancer.

Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells.

Artesunate is a kind of derivative of artemisinin, which possesses potent anti-cancer effect in addition to its anti-malarial property. And autophagy was a highly conserved process, exerting a double-edged effect in cancer cell survival. Besides, apoptosis is a programmed cell death program, crucial to cell homeostasis. However, the relations between autophagy and apoptosis, and the role of artesunate in this interaction have not been elucidated in bladder cancer. In present study, we used human bladder cancer cells (T24 and EJ cell lines) to investigate that how artesunate would influence autophagy and apoptosis processes. We found that artesunate could inhibit the viability, proliferation and migration of bladder cancer cells, as well as induce autophagy in a time and dose dependent manner, in addition, the artesunate induced autophagy subsequently activated cells apoptosis. Furthermore, we pretreated T24 and EJ cells with 3-Methyladenine or Rapamycin to inhibit or promote autophagy, respectively, leading to inhibited or increased apoptosis. Moreover, pretreatment of these cell lines with Acadesine or Dorsomorphin to activate or inhibit the AMPK-mTOR-ULK1 pathway, respectively, also resulting in promotion or suppression in both autophagy and apoptosis. In the upstream, ROS upregulation triggered by ART initiated AMPK-mTOR-ULK1 axis. However, this initiative effect of ROS can be reversed by N-Acetyl-l-cysteine. Therefore, this study indicated that Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells.

Sodium butyrate inhibits migration and induces AMPK-mTOR pathway-dependent autophagy and ROS-mediated apoptosis via the miR-139-5p/Bmi-1 axis in human bladder cancer cells.

Bladder cancer is one of the most frequently occurring malignant tumors in the urinary system. Sodium butyrate (NaB) is a histone deacetylase inhibitor and exerts remarkable antitumor effects in various cancer cells. MicroRNAs (miRNAs) and autophagy play crucial roles in cancer occurrence and development. In the present study, we evaluated the anticancer effects, including cell migration inhibition and the apoptotic effects of NaB in human bladder cancer cells. Furthermore, we found that NaB inhibited migration and induced AMPK/mTOR pathway-activated autophagy and reactive oxygen species (ROS) overproduction via the miR-139-5p/Bmi-1 axis. In addition, we found that ROS overproduction contributed to NaB-induced caspase-dependent apoptosis and autophagy. The interplay between autophagy and apoptosis in NaB treatment was clarified. Our findings provide a further understanding of EMT reversion, apoptosis and autophagy induced by antitumor drugs and a novel perspective and alternative strategy for bladder cancer chemotherapy.

Clinicopathological and prognostic significance of preoperative plasma fibrinogen level in patients with upper urinary tract urothelial carcinoma: A retrospective tumor marker prognostic study.

PURPOSE: To retrospectively evaluate the prognostic value of preoperative plasma fibrinogen to predict oncological outcome and intravesical recurrence in upper urinary tract urothelial carcinoma. METHODS: This retrospective study comprised 130 patients with non-metastatic upper urinary tract urothelial carcinoma who underwent surgery between June 2009 and June 2017 at a single center. Patients were categorized base on an optimal value of preoperative plasma fibrinogen. Progression-free and cancer-specific survival were assessed using Kaplan-Meier method. The associations between plasma fibrinogen and clinical outcomes were assessed with univariate and Multivariate analysis. RESULTS: Elevated plasma fibrinogen was associated with advance tumor stage, high tumor grade and tumor size. No significant association was found between plasma fibrinogen and intravesical recurrence. Multivariate analysis revealed that plasma fibrinogen ≥3.602 g/L was an independent prognostic indicator for progression-free survival (HR = 2.18; 95% CI: 1.17-4.06; p = 0.01) and cancer-specific survival (HR = 2.2; 95% CI: 1.13-4.28; p = 0.02), as well as pathological T stage and tumor grade. CONCLUSIONS: Elevated preoperative plasma fibrinogen is an independent unfavorable prognostic factor for oncological outcomes in patients with upper urinary tract urothelial carcinoma. However, there is no association between preoperative plasma fibrinogen and intravesical recurrence. As an effective and easily accessible biomarker, this parameter can be applied in pre-intervention risk stratification of upper urinary tract urothelial carcinoma.

Silencing circular RNA UVRAG inhibits bladder cancer growth and metastasis by targeting the microRNA-223/fibroblast growth factor receptor 2 axis.

Circular RNA UVRAG (circUVRAG), a type of non-coding RNA, is derived and cyclized by part of the exon from the UVRAG gene. However, the role of circUVRAG in bladder cancer (BLCA) has not been reported. The purpose of the present study was therefore to characterize the role of circUVRAG in BLCA. Bioinformatics analysis showed interactive relationships among circUVRAG, microRNA-223 (miR-223), and fibroblast growth factor receptor 2 (FGFR2). Quantitative real-time PCR was used to detect the expression of circUVRAG in BLCA cell lines. UM-UC-3 cells were stably transfected with siRNA against circUVRAG, and cell proliferation and migration ability were tested using the CCK8 assay, clone formation, and Transwell assays in vitro. Tumor xenograft formation and metastasis were determined using nude mice. Fluorescence in situ hybridization was used to confirm the subcellular localization of circUVRAG, and the luciferase reporter assay was used to confirm the relationships among circUVRAG, miR-223, and FGFR2. Results showed that circUVRAG was upregulated in BLCA cell lines. Downregulation of circUVRAG expression suppressed proliferation and metastasis both in vitro and in vivo. Downregulation of circUVRAG suppressed FGFR2 expression by "sponging" miR-223, which was confirmed by rescue experiments and luciferase reporter assay. Overall, the results showed that downregulation of circUVRAG suppressed the aggressive biological phenotype of BLCA. Taken together, silencing circular RNA UVRAG inhibited bladder cancer growth and metastasis by targeting the miR-223/FGFR2 axis, which may provide a potential biomarker and therapeutic target for the management of BLCA.

Spontaneous generation of a novel foetal human retinal pigment epithelium (RPE) cell line available for investigation on phagocytosis and morphogenesis.

OBJECTIVES: Primary retinal pigment epithelium (RPE) cells have a limited capacity to re-establish epithelial morphology and to maintain native RPE function in vitro, and all commercially available RPE cell lines have drawbacks of morphology or function; therefore, the establishment of new RPE cell lines with typical characteristics of RPE would be helpful in further understanding of their physiological and pathological mechanisms. Here, we firstly report a new spontaneously generated RPE line, fhRPE-13A, from a 13-week aborted foetus. We aimed to investigate its availability as a RPE model. MATERIALS AND METHODS: RNA-seq data were mapped to the human genome assembly hg19. Global transcriptional data were analysed by Weighted Gene Co-expression Network Analysis (WGCNA) and differentially expressed genes (DEGs). The morphology and molecular characteristics were examined by immunofluorescence, transmission electron micrographs, PCR and western blot. Photoreceptor outer segments (POS) phagocytosis assay and transepithelial resistance measurement (TER) were performed to assess phagocytic activity and barrier function, respectively. RESULTS: The fhRPE-13A cells showed typical polygonal morphology and normal biological processes of RPE. Meanwhile they were capable of POS phagocytosis in vitro, and the expression level of TYR and TYRP1 were significantly higher than that in ARPE-19 cells. CONCLUSIONS: The foetal human RPE line fhRPE-13A is a valuable system for researching phagocytosis and morphogenesis of RPE in vitro.