Fluorinated Polyimide Tunneling Layer for Efficient and Stable Perovskite Photovoltaics.

Despite the remarkable progress of perovskite solar cells (PSCs), challenges remain in terms of finding effective and viable strategies to enhance their long-term stability while maintaining high efficiency. In this study, a new insulating and hydrophobic fluorinated polyimide (FPI: 6FDA-6FAPB) was used as the interface layer between the perovskite layer and the hole transport layer (HTL) in PSCs. The functional groups of FPI play a pivotal role in passivating interface defects within the device. Due to its high work function, FPI demonstrates field-effect passivation (FEP) capabilities as an interface layer, effectively mitigating non-radiative recombination at the interface. Notably, the FPI insulating interface layer does not impede carrier transmission at the interface, which is attributed to the presence of hole tunneling effects. The optimized PSCs achieve an outstanding power conversion efficiency (PCE) of 24.61 % and demonstrate excellent stability, showcasing the efficacy of FPI in enhancing device performance and reliability.

Development and validation of cancer-associated fibroblasts-related gene landscape in prognosis and immune microenvironment of bladder cancer.

Backgrounds: Bladder cancer (BLCA) is one of the most prevalent cancers of the genitourinary system, the clinical outcomes of patients with BLCA are bad, and the morbidity rate is high. One of the key components of the tumor microenvironment (TME) is cancer-associated fibroblasts (CAFs) which are critically involved in BLCA tumorigenesis. Previous studies have shown the involvement of CAFs in tumor growth, cancer progression, immune evasion, angiogenesis, and chemoresistance in several cancers such as breast, colon, pancreatic, ovarian, and prostate cancers. However, only a few studies have shown the role of CAFs in the occurrence and development of BLCA. Methods: We have retrieved and merged the data on RNA-sequencing of patients with BLCA from databases including "the Cancer Genome Atlas" and "Gene Expression Omnibus." Next, we compared the differences in CAFs-related genes (CRGs) expression between normal and BLCA tissues. Based on CRGs expression, we randomly divided patients into two groups. Next, we determined the correlation between CAFs subtypes and differentially expressed CRGs (DECRGs) between the two subtypes. Furthermore, the "Gene Ontology" and "Kyoto Encyclopedia of Genes and Genomes pathway" enrichment analyses were conducted to determine the functional characteristics between the DECRGs and clinicopathology. Results: We identified five genes (POF1B, ARMCX1, ALDOC, C19orf33, and KRT13) using multivariate COX regression and "Least Absolute Shrinkage and Selection Operator (LASSO) COX regression analysis" for developing a prognostic model and calculating the CRGs-risk score. The TME, mutation, CSC index, and drug sensitivity were also analyzed. Conclusion: We constructed a novel five- CRGs prognostic model, which sheds light on the roles of CAFs in BLCA.

Improving Crystallization and Stability of Perovskite Solar Cells Using a Low-Temperature Treated A-Site Cation Solution in the Sequential Deposition.

The two-step sequential deposition is a commonly used method by researchers for fabricating perovskite solar cells (PSCs) due to its reproducibility and tolerant preparation conditions. However, the less-than-favorable diffusive processes in the preparation process often result in subpar crystalline quality in the perovskite films. In this study, we employed a simple strategy to regulate the crystallization process by lowering the temperature of the organic-cation precursor solutions. By doing so, we minimized interdiffusion processes between the organic cations and pre-deposited lead iodide (PbI2) film under poor crystallization conditions. This allowed for a homogenous perovskite film with improved crystalline orientation when transferred to appropriate environmental conditions for annealing. As a result, a boosted power conversion efficiency (PCE) was achieved in PSCs tested for 0.1 cm2 and 1 cm2, with the former exhibiting a PCE of 24.10% and the latter of 21.56%, compared to control PSCs, which showed a PCE of 22.65% and 20.69%, respectively. Additionally, the strategy increased device stability, with the cells holding 95.8% and 89.4% of the initial efficiency even after 7000 h of aging under nitrogen or 20-30% relative humidity and 25 °C. This study highlights a promising low-temperature-treated (LT-treated) strategy compatible with other PSCs fabrication techniques, adding a new possibility for temperature regulation during crystallization.

YTHDF1 Promotes Bladder Cancer Cell Proliferation via the METTL3/YTHDF1-RPN2-PI3K/AKT/mTOR Axis.

N6-methyladenosine (m6A) is the most common mRNA modification and it plays a critical role in tumor progression, prognoses and therapeutic response. In recent years, more and more studies have shown that m6A modifications play an important role in bladder carcinogenesis and development. However, the regulatory mechanisms of m6A modifications are complex. Whether the m6A reading protein YTHDF1 is involved in the development of bladder cancer remains to be elucidated. The aims of this study were to determine the association between METTL3/YTHDF1 and bladder cancer cell proliferation and cisplatin resistance to explore the downstream target genes of METTL3/YTHDF1 and to explore the therapeutic implications for bladder cancer patients. The results showed that the reduced expression of METTL3/YTHDF1 could lead to decreased bladder cancer cell proliferation and cisplatin sensitivity. Meanwhile, overexpression of the downstream target gene, RPN2, could rescue the effect of reduced METTL3/YTHDF1 expression on bladder cancer cells. In conclusion, this study proposes a novel METTL3/YTHDF1-RPN2-PI3K/AKT/mTOR regulatory axis that affects bladder cancer cell proliferation and cisplatin sensitivity.

SIRT1 Promotes Cisplatin Resistance in Bladder Cancer via Beclin1 Deacetylation-Mediated Autophagy.

Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant T24/DDP cell line to investigate this mechanism. The apoptosis rate and cell viability were assessed using flow cytometry and the CCK8 method. The expression levels of the relevant RNA and protein were determined using RT-qPCR and a Western blot analysis, respectively. Immunoprecipitation was utilized to validate the interaction between SIRT1 and Beclin1, as well as to determine the acetylation level of Beclin1. The findings indicated the successful construction of the T24/DDP cell line, which exhibited autophagy-dependent cisplatin resistance. Inhibiting autophagy significantly reduced the drug resistance index of these cells. The T24/DDP cell line showed a high SIRT1 expression level. The overexpression of SIRT1 activated autophagy, thereby further promoting cisplatin resistance in the T24/DDP cell line. Conversely, inhibiting autophagy counteracted the cisplatin-resistance-promoting effects of SIRT1. Silencing SIRT1 led to increased acetylation of Beclin1, the inhibition of autophagy, and a reduction in the cisplatin resistance of the T24/DDP cell line. Introducing a double mutation (lysine 430 and 437 to arginine, 2KR) in Beclin-1 inhibited acetylation and activated autophagy, effectively reversing the decreased cisplatin resistance resulting from SIRT1 silencing. In summary, our study elucidated that SIRT1 promotes cisplatin resistance in human bladder cancer T24 cells through Beclin1-deacetylation-mediated autophagy activation. These findings suggest a potential new strategy for reversing cisplatin resistance in bladder cancer.

A novel 7­hypoxia­related long non­coding RNA signature associated with prognosis and proliferation in melanoma.

Hypoxia­related long non­coding RNAs (lncRNAs) are important indicators of the poor prognosis of cancers. The present study aimed to explore the potential relationship between melanoma and hypoxia­related lncRNAs. The transcriptome and clinical data of patients with melanoma were downloaded from The Cancer Genome Atlas database. The prognostic hypoxia­related lncRNAs were screened out using Pearson's correlation test and univariate Cox analysis. As a result, a hypoxia­related­lncRNA signature based on the expression of 7 lncRNAs was constructed, with one unfavourable [MIR205 host gene (MIR205HG)] and six favourable (T cell receptor ß variable 11­2, HLA­DQB1 antisense RNA 1, AL365361.1, AC004847.1, ubiquitin specific peptidase 30 antisense RNA 1 and AC022706.1) lncRNAs as prognostic factors for melanoma. Patients with melanoma were divided into high­ and low­risk groups based on the risk score obtained. Survival analyses were performed to assess the prognostic value of the present risk model. Potential tumour­associated biological pathways associated with the present signature were explored using gene set enrichment analysis. The CIBERSORT algorithm demonstrated the important role of the hypoxia­related lncRNAs in regulating tumour­infiltrating immune cells. Clinical samples collected from our center partly confirmed our findings. Cell Counting Kit­8 and flow cytometry assays indicated the suppression of proliferation of melanoma cells following inhibition of MIR205HG expression. Indicators of the canonical Wnt/ß­catenin signalling pathway were detected by western blotting. The present study demonstrated that MIR205HG could promote melanoma cell proliferation partly via the canonical Wnt/ß­catenin signalling pathway. These findings indicated a 7­hypoxia­related­lncRNA signature that can serve as a novel predictor of melanoma prognosis.

Stable and rapid partial nitrification achieved by boron stimulating autoinducer-2 mediated quorum sensing at room & low temperature.

The stable and rapid initiation of partial nitrification is a long-term interest of researchers. In this study, boron, an activator of autoinducer-2 (AI-2), was first proposed to promote partial nitrification and improve sludge properties. Two concentrations of boron were added to six laboratory-scale nitrification reactors to study the effects of boron stimulated AI-2-mediated quorum sensing on nitrification at room and low temperature. Boron could significantly increase the concentration of AI-2 in the reactor (p < 0.05), and the high concentration of boron showed better performance at two temperatures. The realization of partial nitrification was mainly due to the accumulation of NO2-- N promoted by the increase of AI-2 concentration. NO2-- N accumulation occurred in all the boron-treated reactors, while no NO2-- N accumulation occurred in the reactor without boron at room temperature or the accumulation efficiency was 14% lower at low temperature. Community analysis and qPCR further confirmed that exogenous boron had no significant effect on AOB, but inhibited NOB, especially at room temperature. The changes of EPS were slightly different at the two temperatures: at room temperature, boron increased the total EPS production, while at low temperature it mainly changed the PN/PS value of EPS. It was worth noting that the effect of boron on partial nitrification depended not only on its concentration, but also on NH4+-N concentration and temperature. This study provided a new strategy for the rapid and stable initiation of partial nitrification process.

PP2A promotes apoptosis and facilitates docetaxel sensitivity via the PP2A/p-eIF4B/XIAP signaling pathway in prostate cancer.

Serine/threonine protein phosphatase 2A (PP2A) is a protein that has a wide range of biological functions. As prostate cancer progresses from hormone-sensitive prostate cancer to castration-resistant prostate cancer (CRPC), the expression level of PP2A has been found to decrease. The present study aimed to determine the roles that PP2A may play in prostate cancer and its association with the downstream factor, X-linked inhibitor of apoptosis (XIAP). First, the mRNA and protein expression levels of PP2A in LNCaP, DU145 and PC-3 prostate cancer cell lines were measured. Next, the population of PP2A heterodimers was increased using a PP2A agonist, DT061, in the DU145 and PC-3 cell lines. PP2A expression was then knocked down in the LNCaP cell line. Western blot analysis was performed to determine the association between PP2A, phosphorylated (p)-eukaryotic initiation factor 4B (eIF4B) and XIAP. The results revealed that following the increase in PP2A expression, the DU145 and PC-3 cell lines were more sensitive to docetaxel according to Cell Counting Kit-8 assays and had an increased apoptotic rate as assessed by flow cytometry. Conversely, following the transfection of small interfering (si)PP2A into the LNCaP cell line, the sensitivity to docetaxel decreased, as well as the apoptotic rate. In addition, following treatment with the PP2A agonist, DT061, PP2A expression was found to be significantly upregulated, while p-eIF4B and XIAP protein expression levels were significantly downregulated. By contrast, following the transfection of siPP2A into the LNCaP cell line, PP2A protein expression levels were found to be downregulated, while p-eIF4B and XIAP expression levels were significantly upregulated. In conclusion, by affecting the downstream factor XIAP, PP2A may play a key role in promoting apoptosis and facilitating docetaxel sensitivity in prostate cancer cell lines.

Hot-Air Treatment-Regulated Diffusion of LiTFSI to Accelerate the Aging-Induced Efficiency Rising of Perovskite Solar Cells.

Perovskite solar cells (PSCs) with LiTFSI-doped Spiro-OMeTAD as the hole transport layer (HTL) generally require aging in the air to achieve high efficiency (a.k.a. aging-induced efficiency rising), but attention is rarely paid to the synergistic effects of temperature and humidity during the ambient aging. In this work, based on the understanding of the doping mechanism of Spiro-OMeTAD, we develop an ambient condition-controlled hot-air treatment (HAT) for such kinds of PSCs to further improve the device efficiency and relieve the photocurrent hysteresis. After storing the PSCs at a temperature of 35-40 °C and humidity of 35-40% RH for 30 min, efficient redistribution of LiTFSI in Spiro-OMeTAD enables much-increased conductivity due to the increased concentration of Spiro-OMeTAD+·O2- and Spiro-OMeTAD+·TFSI-, leading to an enhanced fill factor. From the light intensity-dependent Voc and capacitance-voltage measurements, the Voc enhancement is proven to be originated from the change in dominant recombination type from trap-assisted interfacial recombination to bulk Shockley-Read-Hall recombination and the improved carrier dynamics at the perovskite/HTL interface. Furthermore, the decreased density and migration of shallow-level charge traps result in the negligible hysteresis of treated devices. Our work provides new insights into the effect of ambient aging on PSCs with Spiro-OMeTAD and reveals the potentials of HAT to improve the device performance.

EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation.

Bladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signaling pathways. However, the role of the EGF-SHCBP1 axis in bladder cancer progression remains unexplored. Herein, we report that SHCBP1 is upregulated in bladder cancer tissues and cells, with cytoplasmic or nuclear localization. Released SHCBP1 responds to EGF stimulation by translocating into the nucleus following Ser273 phosphorylation. Depletion of SHCBP1 reduces EGF-induced cell migration and invasiveness of bladder cancer cells. Mechanistically, SHCBP1 binds to RACGAP1 via its N-terminal domain of amino acids 1 ~ 428, and this interaction is enhanced following EGF treatment. Furthermore, SHCBP1 facilitates cell migration by inhibiting RACGAP-mediated GTP-RAC1 inactivation, whose activity is indispensable for cell movement. Collectively, we demonstrate that the EGF-SHCBP1-RACGAP1-RAC1 axis acts as a novel regulatory mechanism of bladder cancer progression, which offers a new clinical therapeutic strategy to combat bladder cancer.

Starvation induced autophagy promotes the progression of bladder cancer by LDHA mediated metabolic reprogramming.

BACKGROUND: Aberrant autophagy and preternatural elevated glycolysis are prevalent in bladder cancer (BLCA) and are both related to malignant progression. However, the regulatory relationship between autophagy and glycolytic metabolism remains largely unknown. We imitated starvation conditions in the tumour microenvironment and found significantly increased levels of autophagy and aerobic glycolysis, which both regulated the progression of BLCA cells. We further explored the regulatory relationships and mechanisms between them. METHODS: We used immunoblotting, immunofluorescence and transmission electron microscopy to detect autophagy levels in BLCA cells under different treatments. Lactate and glucose concentration detection demonstrated changes in glycolysis. The expression of lactate dehydrogenase A (LDHA) was detected at the transcriptional and translational levels and was also silenced by small interfering RNA, and the effects on malignant progression were further tested. The underlying mechanisms of signalling pathways were evaluated by western blot, immunofluorescence and immunoprecipitation assays. RESULTS: Starvation induced autophagy, regulated glycolysis by upregulating the expression of LDHA and caused progressive changes in BLCA cells. Mechanistically, after starvation, the ubiquitination modification of Axin1 increased, and Axin1 combined with P62 was further degraded by the autophagy-lysosome pathway. Liberated ß-catenin nuclear translocation increased, binding with LEF1/TCF4 and promoting LDHA transcriptional expression. Additionally, high expression of LDHA was observed in cancer tissues and was positively related to progression. CONCLUSION: Our study demonstrated that starvation-induced autophagy modulates glucose metabolic reprogramming by enhancing Axin1 degradation and ß-catenin nuclear translocation in BLCA, which promotes the transcriptional expression of LDHA and further malignant progression.

SPHK1 contributes to cisplatin resistance in bladder cancer cells via the NONO/STAT3 axis.

Sphingosine­1­phosphate (S1P) serves an important role in various physiological and pathophysiological processes, including the regulation of cell apoptosis, proliferation and survival. Sphingosine kinase 1 (SPHK1) is a lipid kinase that phosphorylates sphingosine to generate S1P. S1P has been proven to be positively correlated with chemotherapy resistance in breast cancer, colorectal carcinoma and non­small cell lung cancer. However, whether SPHK1 is involved in the development of cisplatin resistance remains to be elucidated. The present study aimed to identify the association between SPHK1 and chemoresistance in bladder cancer cells and to explore the therapeutic implications in patients with bladder cancer. Bladder cancer cell proliferation and apoptosis were determined using Cell Counting Kit­8 assays and flow cytometry, respectively. Apoptosis­related proteins were detected via western blotting. The results revealed that SPHK1 was positively correlated with cisplatin resistance in bladder cancer cells, exhibiting an antiapoptotic effect that was reflected by the downregulation of apoptosis­related proteins (Bax and cleaved caspase­3) and the upregulation of an antiapoptotic protein (Bcl­2) in SPHK1­overexpression cell lines. Suppression of SPHK1 by small interfering RNA or FTY­720 significantly reversed the antiapoptotic effect. A potential mechanism underlying SPHK1­induced cisplatin resistance and apoptosis inhibition may be activation of STAT3 via binding non­POU domain containing octamer binding. In conclusion, the present study suggested that SPHK1 displayed significant antiapoptotic effects in cisplatin­based treatment, thus may serve as a potential novel therapeutic target for the treatment for bladder cancer.

A Glycolysis-Based Long Non-coding RNA Signature Accurately Predicts Prognosis in Renal Carcinoma Patients.

BACKGROUND: The prognosis of renal cell carcinoma (RCC) varies greatly among different risk groups, and the traditional indicators have limited effect in the identification of risk grade in patients with RCC. The purpose of our study is to explore a glycolysis-based long non-coding RNAs (lncRNAs) signature and verify its potential clinical significance in prognostic prediction of RCC patients. METHODS: In this study, RNA data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate cox regression displayed six significantly related lncRNAs (AC124854.1, AC078778.1, EMX2OS, DLGAP1-AS2, AC084876.1, and AC026401.3) which were utilized in construction of risk score by a formula. The accuracy of risk score was verified by a series of statistical methods such as receiver operating characteristic (ROC) curves, nomogram and Kaplan-Meier curves. Its potential clinical significance was excavated by gene enrichment analysis. RESULTS: Kaplan-Meier curves and ROC curves showed reliability of the risk score to predict the prognosis of RCC patients. Stratification analysis indicated that the risk score was independent predictor compare to other traditional clinical parameters. The clinical nomogram showed highly rigorous with index of 0.73 and precisely predicted 1-, 3-, and 5-year survival time of RCC patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene set enrichment analysis (GSEA) depicted the top ten correlated pathways in both high-risk group and low-risk group. There are 6 lncRNAs and 25 related mRNAs including 36 lncRNA-mRNA links in lncRNA-mRNA co-expression network. CONCLUSION: This research demonstrated that glycolysis-based lncRNAs possessed an important value in survival prediction of RCC patients, which would be a potential target for future treatment.

Identification of a Three-Glycolysis-Related lncRNA Signature Correlated With Prognosis and Metastasis in Clear Cell Renal Cell Carcinoma.

The clear cell renal cell carcinoma (ccRCC) is not only a malignant disease but also an energy metabolic disease, we aimed to identify a novel prognostic model based on glycolysis-related long non-coding RNA (lncRNAs) and explore its mechanisms. With the use of Pearson correlation analysis between the glycolysis-related differentially expressed genes and lncRNAs from The Cancer Genome Atlas (TCGA) dataset, we identified three glycolysis-related lncRNAs and successfully constructed a prognostic model based on their expression. The diagnostic efficacy and the clinically predictive capacity of the signature were evaluated by univariate and multivariate Cox analyses, Kaplan-Meier survival analysis, and principal component analysis (PCA). The glycolysis-related lncRNA signature was constructed based on the expressions of AC009084.1, AC156455.1, and LINC00342. Patients were grouped into high- or low-risk groups according to risk score demonstrated significant differences in overall survival (OS) period, which were validated by patients with ccRCC from the International Cancer Genome Consortium (ICGC) database. Univariate Cox analyses, multivariate Cox analyses, and constructed nomogram-confirmed risk score based on our signature were independent prognosis predictors. The CIBERSORT algorithms demonstrated significant correlations between three-glycolysis-related lncRNAs and the tumor microenvironment (TME) components. Functional enrichment analysis demonstrated potential pathways and processes correlated with the risk model. Clinical samples validated expression levels of three-glycolysis-related lncRNAs, and LINC00342 demonstrated the most significant aberrant expression. in vitro, the general overexpression of LINC00342 was detected in ccRCC cells. After silencing LINC00342, the aberrant glycolytic levels and migration abilities in 786-O cells were decreased significantly, which might be explained by suppressed Wnt/ß-catenin signaling pathway and reversed Epithelial mesenchymal transformation (EMT) process. Collectively, our research identified a novel three-glycolysis-related lncRNA signature as a promising model for generating accurate prognoses for patients with ccRCC, and silencing lncRNA LINC00342 from the signature could partly inhibit the glycolysis level and migration of ccRCC cells.

An epithelial-mesenchymal transition-related long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer.

Bladder cancer is a common malignant tumour worldwide. Epithelial-mesenchymal transition (EMT)-related biomarkers can be used for early diagnosis and prognosis of cancer patients. To explore, accurate prediction models are essential to the diagnosis and treatment for bladder cancer. In the present study, an EMT-related long noncoding RNA (lncRNA) model was developed to predict the prognosis of patients with bladder cancer. Firstly, the EMT-related lncRNAs were identified by Pearson correlation analysis, and a prognostic EMT-related lncRNA signature was constructed through univariate and multivariate Cox regression analyses. Then, the diagnostic efficacy and the clinically predictive capacity of the signature were assessed. Finally, Gene set enrichment analysis (GSEA) and functional enrichment analysis were carried out with bioinformatics. An EMT-related lncRNA signature consisting of TTC28-AS1, LINC02446, AL662844.4, AC105942.1, AL049840.3, SNHG26, USP30-AS1, PSMB8-AS1, AL031775.1, AC073534.1, U62317.2, C5orf56, AJ271736.1, and AL139385.1 was constructed. The diagnostic efficacy of the signature was evaluated by the time-dependent receiver-operating characteristic (ROC) curves, in which all the values of the area under the ROC (AUC) were more than 0.73. A nomogram established by integrating clinical variables and the risk score confirmed that the signature had a good clinically predict capacity. GSEA analysis revealed that some cancer-related and EMT-related pathways were enriched in high-risk groups, while immune-related pathways were enriched in low-risk groups. Functional enrichment analysis showed that EMT was associated with abundant GO terms or signaling pathways. In short, our research showed that the 14 EMT-related lncRNA signature may predict the prognosis and progression of patients with bladder cancer.

Fetuin B overexpression suppresses proliferation, migration, and invasion in prostate cancer by inhibiting the PI3K/AKT signaling pathway.

Fetuin B (FETUB) is a glycoprotein that is a member of the cysteine protease inhibitor family, and it is associated with cancer. However, the role of FETUB in prostate carcinogenesis is unknown. In this study, we overexpressed FETUB in prostate cancer cells by using lentivirus and then studied the impacts on cell apoptosis, migration and invasion. We found that apoptosis was increased and the migration and invasion of prostate cancer cells were significantly inhibited after overexpression. Then, we performed experiments in vivo and found that there were fewer tumors in the overexpression groups than in the control groups. In addition, we demonstrated that overexpression of FETUB inactivates the PI3K/AKT signaling pathway. Rescue assays revealed that intervention of 740Y-P reversed the anti-tumor effect of FETUB on prostate cancer cells. Taken together, our results revealed that FETUB may act as a novel regulator to promote apoptosis and inhibit the migration and invasion of prostate cancer cells and that FETUB is related to the inactivation of the PI3K/AKT signaling pathway.

Nucleolar and Spindle Associated Protein 1 (NUSAP1) Promotes Bladder Cancer Progression Through the TGF-ß Signaling Pathway.

PURPOSE: NUSAP1 has been reported to be involved in the progression of several types of cancer. However, its expression and exact role in bladder cancer (BLCA) remains elusive. The aim of this study was to determine the expression and role of NUSAP1 in BLCA. METHODS: Tissue microarray, real-time PCR, Western blot and immunohistochemistry assays were carried out to determine NUSAP1 expression in BLCA tissues and cells. The biological roles of NUSAP1 were investigated using CCK-8, EdU labeling, flow cytometry, Transwell, and wound healing assays. Additionally, the effect of NUSAP1 on epithelial-mesenchymal transition (EMT) was investigated by Western blotting and real-time PCR. RESULTS: We found that NUSAP1 was upregulated in BLCA, and its expression was closely related to the poor prognosis of patients. Subsequently, we transfected 5637 and T24 cell lines with NUSAP1 siRNA and an NUSAP1 overexpression plasmid, respectively. NUSAP1 downregulation in 5637 cells inhibited cell proliferation, migration, and invasiveness and enhanced chemosensitivity to gemcitabine, while NUSAP1 overexpression in T24 cells resulted in the inverse effects. Moreover, NUSAP1 regulated EMT via the TGF-ß signaling pathway, and when TGF-beta receptor 1 (TGFBR1) was inhibited with the inhibitor SB525334, the invasion and metastasis ability of BLCA cells was significantly suppressed, as well as p-Smad2/3 and vimentin expression. CONCLUSION: Our above data demonstrate that NUSAP1 contributes to BLCA progression via the TGF-ß signaling pathway.