The potential of organoids in renal cell carcinoma research.

Renal cell carcinoma, a leading cause of death in urological malignancies, arises from the nephron. Its characteristics include diversity in disease biology, varied clinical behaviors, different prognoses, and diverse responses to systemic therapies. The term 'organoids' is used to describe structures resembling tissues created through the three-dimensional cultivation of stem cells in vitro. These organoids, when derived from tumor tissues, can retain the diversity of the primary tumor, mirror its spatial tissue structure, and replicate similar organ-like functions. In contrast to conventional two-dimensional cell cultures and the transplantation of tumor tissues into other organisms, organoids derived from tumors maintain the complexity and microenvironment of the original tumor tissue. This fidelity makes them a more reliable model for the development of cancer drugs, potentially accelerating the translation of these drugs to clinical use and facilitating personalized treatment options for patients. This review aims to summarize the recent advancements in the use of organoids for studying renal cell carcinoma, focusing on their cultivation, potential applications, and inherent limitations.

Evaluation of Real-time 3-dimensional Echocardiography Parameters for In-stent Restenosis after Percutaneous Coronary Intervention for Myocardial Infarction.

Objective: To analyze the role of real-time 3-dimensional echocardiography (RT-3DE) in evaluating in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Methods: This study enrolled 62 AMI patients (research group) and 51 healthy volunteers (control group) who presented to The First Affiliated Hospital of Zhejiang University between October 2021 and December 2022. Differences in RT-3DE parameters between the two groups and changes in RT-3DE parameters before and after PCI in the research group were compared. The patients were followed up for 6 months after PCI to analyze the evaluation effect of RT-3DE parameters on post-PCI ISR. Results: After PCI, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), displacement standard deviation (Esd) in both groups, maximum displacement value (Emax), and LV synchronization parameters were all reduced and were higher in the study group than in the control group (P < .05). The left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR), average motion amplitude (Eavg), minimum displacement value (Emin), and left ventricular synchronization parameters were all lower in the study group than in the control group (P < .05). The LVEDV and Tmsv16-SD/R-R were found to be higher in patients with ISR 6 months after PCI than in those without ISR, while LVEF and Emin were lower (P < .05). ROC curve analysis revealed that all four parameters exhibited excellent prediction efficiency for the occurrence of ISR, among which LVEF had the best performance. Conclusions: RT-3DE parameters play an excellent role in predicting the occurrence of post-PCI ISR in AMI patients.

Advances in tumor microenvironment and underlying molecular mechanisms of bladder cancer: a systematic review.

Bladder cancer is one of the most frequent malignant tumors of the urinary system. The prevalence of bladder cancer among men and women is roughly 5:2, and both its incidence and death have been rising steadily over the past few years. At the moment, metastasis and recurrence of advanced bladder cancer-which are believed to be connected to the malfunction of multigene and multilevel cell signaling network-remain the leading causes of bladder cancer-related death. The therapeutic treatment of bladder cancer will be greatly aided by the elucidation of these mechanisms. New concepts for the treatment of bladder cancer have been made possible by the advancement of research technologies and a number of new treatment options, including immunotherapy and targeted therapy. In this paper, we will extensively review the development of the tumor microenvironment and the possible molecular mechanisms of bladder cancer.

Perfusion drugs for non­muscle invasive bladder cancer (Review).

The high recurrence rate and poor prognosis of non-muscle invasive bladder cancer (BC) are challenges that need to be urgently addressed. Transurethral cystectomy for bladder tumors is often combined with bladder perfusion therapy, which can effectively reduce the recurrence and progression rates of BC. The present review integrated and analyzed currently available bladder perfusion drugs, mainly including chemotherapeutic agents, immunotherapeutic agents and other adjuvant perfusion drugs. Bacillus Calmette-Guerin (BCG) perfusion was the pioneering immunotherapy for early BC and still ranks high in the selection of perfusion drugs. However, BCG infusion has a high toxicity profile and has been shown to be ineffective in some patients. Due to the limitations of BCG, new bladder perfusion drugs are constantly being developed. Immunotherapeutic agents have opened a whole new chapter in the selection of therapeutic agents for bladder perfusion. The present review explored the mechanism of action, clinical dosage and adverse effects of a variety of bladder perfusion drugs currently in common use, described combined perfusion and compared the effects of certain drugs on BC.

Biomechanical characteristics of arteries during pelvic fracture reduction and dynamic simulation analysis.

During robot-assisted reduction of pelvic fracture, blood vessels are susceptible to tensile and shear forces, making them prone to injury. Considering the impact of pelvic reduction on the risk of arterial injury, the biomechanical characteristics of arteries during the pelvic fracture reduction process are studied, and a refined coupled composite model of the damaged pelvic structure is established. Dynamic simulations of pelvic fracture reduction are conducted based on the planned reduction path. The simulation results show that during the reduction process, when the affected side is rotated, the stress and strain of the artery are maximum, particularly at the locations of the iliac common artery, internal iliac artery, and the superior gluteal artery arch endure significant stress and strain. After reduction, the maximum stress is observed in the right superior gluteal artery, and the maximum strain occurs at the intersection of the right iliac common artery. The stretch ratio of both the left and right iliac common arteries is considerable. Therefore, it can be concluded that the superior gluteal artery and the internal iliac artery are prone to injury, particularly the segment from the origin of the superior gluteal artery to its passage around the greater sciatic notch. After reduction, substantial traction on the iliac common artery, which makes it more susceptible to deformation, carries a risk of arterial rupture and aneurysm formation. This study provides a reference for planning the safe reduction path of pelvic fracture surgery and improving safety.

Neurotrophin-3 from the dentate gyrus supports postsynaptic sites of mossy fiber-CA3 synapses and hippocampus-dependent cognitive functions.

At the center of the hippocampal tri-synaptic loop are synapses formed between mossy fiber (MF) terminals from granule cells in the dentate gyrus (DG) and proximal dendrites of CA3 pyramidal neurons. However, the molecular mechanism regulating the development and function of these synapses is poorly understood. In this study, we showed that neurotrophin-3 (NT3) was expressed in nearly all mature granule cells but not CA3 cells. We selectively deleted the NT3-encoding Ntf3 gene in the DG during the first two postnatal weeks to generate a Ntf3 conditional knockout (Ntf3-cKO). Ntf3-cKO mice of both sexes had normal hippocampal cytoarchitecture but displayed impairments in contextual memory, spatial reference memory, and nest building. Furthermore, male Ntf3-cKO mice exhibited anxiety-like behaviors, whereas female Ntf3-cKO showed some mild depressive symptoms. As MF-CA3 synapses are essential for encoding of contextual memory, we examined synaptic transmission at these synapses using ex vivo electrophysiological recordings. We found that Ntf3-cKO mice had impaired basal synaptic transmission due to deficits in excitatory postsynaptic currents mediated by AMPA receptors but normal presynaptic function and intrinsic excitability of CA3 pyramidal neurons. Consistent with this selective postsynaptic deficit, Ntf3-cKO mice had fewer and smaller thorny excrescences on proximal apical dendrites of CA3 neurons and lower GluR1 levels in the stratum lucidum area where MF-CA3 synapses reside but normal MF terminals, compared with control mice. Thus, our study indicates that NT3 expressed in the dentate gyrus is crucial for the postsynaptic structure and function of MF-CA3 synapses and hippocampal-dependent memory.

Genetic Dissection of BDNF and TrkB Expression in Glial Cells.

The brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase receptor B (TrkB) are widely expressed in the central nervous system. It is well documented that neurons express BDNF and full-length TrkB (TrkB.FL) as well as a lower level of truncated TrkB (TrkB.T). However, there are conflicting reports regarding the expression of BDNF and TrkB in glial cells, particularly microglia. In this study, we employed a sensitive and reliable genetic method to characterize the expression of BDNF and TrkB in glial cells in the mouse brain. We utilized three Cre mouse strains in which Cre recombinase is expressed in the same cells as BDNF, TrkB.FL, or all TrkB isoforms, and crossed them to Cre-dependent reporter mice to label BDNF- or TrkB-expressing cells with soma-localized EGFP. We performed immunohistochemistry with glial cell markers to examine the expression of BDNF and TrkB in microglia, astrocytes, and oligodendrocytes. Surprisingly, we found no BDNF- or TrkB-expressing microglia in examined CNS regions, including the somatomotor cortex, hippocampal CA1, and spinal cord. Consistent with previous studies, most astrocytes only express TrkB.T in the hippocampus of adult brains. Moreover, there are a small number of astrocytes and oligodendrocytes that express BDNF in the hippocampus, the function of which is to be determined. We also found that oligodendrocyte precursor cells, but not mature oligodendrocytes, express both TrkB.FL and TrkB.T in the hippocampus of adult mice. These results not only clarify the expression of BDNF and TrkB in glial cells but also open opportunities to investigate previously unidentified roles of BDNF and TrkB in astrocytes and oligodendrocytes.

Targeting the prostate tumor microenvironment by plant-derived natural products.

Prostate cancer is among the most common malignancies for men, with limited therapy options for last stages of the tumor. There are some different options for treatment and control of prostate tumor growth. However, targeting some specific molecules and cells within tumors has been attracted interests in recent years. The tumor microenvironment (TME) has an important role in the initiation of various malignancies, which can also expand the progression of tumor and facilitate invasion of malignant cells. By regulating immune responses and distinct changes in the metabolism of cells in the tumor, TME has substantial effects in the resistance of cancer cells to therapy. TME in various solid cancers like prostate cancer includes various cells, including cancer cells, supportive stromal cells, immunosuppressive cells, and anticancer inflammatory cells. Natural products including herbal-derived agents and also other natural compounds have been well studied for their anti-tumor potentials. These compounds may modulate various signaling pathways involved in TME, such as immune responses, the metabolism of cells, epigenetics, angiogenesis, and extracellular matrix (ECM). This paper provides a review of the current knowledge of prostate TME and complex interactions in this environment. Additionally, the potential use of natural products and also nanoparticles loaded with natural products as therapeutic adjuvants on different cells and therapeutic targets within prostate TME will be discussed.

Genetic dissection of BDNF and TrkB expression in glial cells.

The brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase receptor B (TrkB) are widely expressed in the central nervous system. It is well documented that neurons express BDNF and full-length TrkB (TrkB.FL), and a lower level of truncated TrkB (TrkB.T). With conflicting results, glial cells also have been reported to express BDNF and TrkB. In the current study, we employed a more sensitive and reliable genetic method to characterize the expression of BDNF and TrkB in glial cells in the mouse brain. We utilized three Cre mouse strains in which Cre recombinase is expressed in the same cells as BDNF, TrkB.FL, or all TrkB isoforms, and crossed them to Cre-dependent EGFP reporter mice to label BDNF- or TrkB- expressing cells. We performed immunohistochemistry with glial cell markers to examine the expression of BDNF and TrkB in microglia, astrocytes, and oligodendrocytes. Surprisingly, we found no BDNF- or TrkB- expressing microglia in the brain and spinal cord. Consistent with previous studies, most astrocytes only express TrkB.T in the adult brain. Moreover, there are a small number of astrocytes and oligodendrocytes that express BDNF, the function of which is to be determined. We also found that oligodendrocyte precursor cells, but not mature oligodendrocytes, express both TrkB.FL and TrkB.T in the adult brain. These results not only clarify the expression of BDNF and TrkB in glial cells, but also open opportunities to investigate previously unidentified roles of BDNF and TrkB in glial cells.

Senescence-related gene c-Myc affects bladder cancer cell senescence by interacting with HSP90B1 to regulate cisplatin sensitivity.

Patients with advanced bladder cancer gradually become less sensitive to chemotherapeutic agents, leading to tumor recurrence. Initiating the senescence program in solid tumors may be an important means of improving short-term drug sensitivity. The important role of c-Myc in bladder cancer cell senescence was determined using bioinformatics methods. The response to cisplatin chemotherapy in bladder cancer sample was analyzed according to the Genomics of Drug Sensitivity in Cancer database. Cell Counting Kit-8 assay, clone formation assay, and senescence-associated ß-galactosidase staining were used to assess bladder cancer cell growth, senescence, and sensitivity to cisplatin, respectively. Western blot and immunoprecipitation were performed to understand the regulation of p21 by c-Myc/HSP90B1. Bioinformatic analysis showed that c-Myc, a cellular senescence gene, was significantly associated with bladder cancer prognosis and sensitivity to cisplatin chemotherapy. c-Myc and HSP90B1 expression were highly correlated in bladder cancer. Reducing the level of c-Myc significantly inhibited bladder cancer cell proliferation, promoted cellular senescence, and enhanced cisplatin chemosensitivity. Immunoprecipitation assays confirmed that HSP90B1 interacted with c-Myc. Western blot analysis showed that reducing the level of HSP90B1 could redeem the p21 overexpression caused by c-Myc overexpression. Further studies showed that reducing HSP90B1 expression could alleviate the rapid growth and accelerate cellular senescence of bladder cancer cells caused by c-Myc overexpression, and that reducing HSP90B1 levels could also improve cisplatin sensitivity in bladder cancer cells. HSP90B1/c-Myc interaction regulates the p21 signaling pathway, which affects cisplatin chemosensitivity by modulating bladder cancer cell senescence.

Tuning active sites for highly efficient bifunctional oxygen electrocatalysts of rechargeable zinc-air battery.

High activity, excellent durability, and low-cost oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) bifunctional catalysts are highly required for rechargeable zinc (Zn)-air batteries. Herein, we designed an electrocatalyst by integrating the ORR active species of ferroferric oxide (Fe3O4) and the OER active species of cobaltous oxide (CoO) into the carbon nanoflower. By well regulating and controlling the synthesis parameters, Fe3O4 and CoO nanoparticles were uniformly inserted into the porous carbon nanoflower. This electrocatalyst can reduce the potential gap between the ORR and OER to 0.79 V. The Zn-air battery assembled with it exhibited an open-circuit voltage of 1.457 V, a stable discharge of 98 h, a high specific capacity of 740 mA h g-1, a large power density of 137 mW cm-2, as well as good charge/discharge cycling performance, exceeding the performance of platinum/carbon (Pt/C). This work provides references for exploring highly efficient non-noble metal oxygen electrocatalysts by tuning ORR/OER active sites.

High throughput assay for compounds that boost BDNF expression in neurons.

Deficiencies in brain-derived neurotrophic factor (BDNF) have been linked to several brain disorders, making compounds that can boost neuronal BDNF synthesis attractive as potential therapeutics. However, a sensitive and quantitative BDNF assay for high-throughput screening (HTS) is still missing. Here we report the generation of a new mouse Bdnf allele, BdnfNLuc, in which the sequence encoding nano luciferase (NLuc) is inserted into the Bdnf locus immediately before the stop codon so that the allele will produce a BDNF-NLuc fusion protein. BDNF-NLuc protein appears to function like BDNF as BdnfNLuc/NLuc homozygous mice grew and behaved almost normally. We were able to establish and optimize cultures of cortical and hippocampal BdnfNLuc/+ neurons isolated from mouse embryos in 384-well plates. We used the cultures as a phenotypic assay to detect the ability of 10 mM KCl to stimulate BDNF synthesis and achieved a reproducible Z' factor > 0.50 for the assay, a measure considered suitable for HTS. We successfully scaled up the assay to screen the 1280-compound LOPAC library (Library of Pharmacologically Active Compounds). The screen identified several BDNF-boosting compounds, one of which is Bay K8644, a L-type voltage-gated calcium channel (L-VGCC) agonist, which was previously shown to stimulate BDNF synthesis. These results indicate that our phenotypic neuronal assay is ready for HTS to identify novel BDNF-boosting compounds.

Study on circumpelvic muscle deformation and dynamic simulation of pelvic fracture reduction.

For the pelvic fracture reduction, generally the fragment of the unaffected side is fixed and the affected side is moved to its correct anatomical position and orientation. During the pelvic fracture reduction, circumpelvic muscles deformation is closely related to the surgical accuracy. In this article, the biomechanical properties of musculoskeletal tissue during pelvic fracture reduction are studied. Five-parameter hyperelastic model named Mooney-Rivlin is adopted to analyze muscle's stress-strain relationship. The finite element model of the injured pelvic musculoskeletal tissue is established, and the deformation of circumpelvic main muscles is simulated. Then, the dynamic simulation of pelvic fracture reduction is performed according to the planned spatial reduction path. The results show that when the muscles are stretched the same stretch length, the strain of the gluteus medius is the largest. It is most prone to deformation under and the muscle injury is most easily to occur. During the pelvic fracture reduction, the strain of gluteus maximus is the largest, and it is most prone to deformation and injury. The traction length is the largest, and the traction force mainly comes from the gluteus maximus. This study provides reference for the robot assisted pelvic fracture reduction.

LncRNA SNHG1 Facilitates Tumor Proliferation and Represses Apoptosis by Regulating PPARγ Ubiquitination in Bladder Cancer.

BACKGROUND: Long noncoding RNAs regulate various biological effects in the progression of cancers. We found that the expression of SNHG1 was significantly up-regulated in bladder cancer after analyzing data obtained from TCGA and GEO. However, the potential role of SNHG1 remains to be investigated in bladder cancer. It was validated that SNHG1 was overexpressed in bladder cancer tissues detected by qRT-PCR and FISH, which was also associated with poor clinical outcome. Additionally, SNHG1 was verified to facilitate tumor proliferation and repress apoptosis in vitro and in vivo. RESULTS: SNHG1 could act as a competitive endogenous RNA and decrease the expression of murine double minute 2 (MDM2) by sponging microRNA-9-3p. Furthermore, MDM2 induced ubiquitination and degradation of PPARγ that contributed to the development of bladder cancer. CONCLUSIONS: the study elucidated that SNHG1 played an important role in bladder cancer and provided a potential therapeutic target for bladder cancer.

Preoperative White Blood Cell-Related Indicators Can Predict the Prognosis of Patients with Transurethral Resection of Bladder Cancer.

Introduction: Numerous studies, including bladder cancer (BLCA), have confirmed the relationship between conventional systemic inflammatory biomarkers and the prognosis of tumors. Leukocytes, as the most common factor in inflammatory indicators, have been reported to predict prognosis in other tumors. However, we have not seen this research in BLCA. Therefore, we aim to find new blood markers to predict the prognosis of patients with transurethral resection of bladder tumor (TURBT). Methods: Two cohorts from the two different hospitals were used for the specific study. The best cutoff values of leukocytes-related indicators were determined according to the ROC curve. Univariate and multivariate Cox regression analysis were used to explore the impact of indicators and clinical features on prognosis for patients with TURBT. The KM curve was used to show the impact of indicators on the prognosis. According to the consequence of multivariate method, a risk model was established to evaluate the prognosis of patients with bladder cancer. Results: The white blood cell-to-lymphocyte ratio (WLR), the white blood cell-to-hemoglobin ratio (WHR), the white blood cell-to-neutrophil ratio (WNR), the white blood cell-to-monocyte ratio (WMR) and the white blood cell-to-erythrocyte ratio (WRR) are related to the prognosis of BLCA. The new risk model consisted of WHR, WMR and platelet-to-lymphocyte ratio (PLR), and patients with TURBT in the high-risk group had a worse prognosis. Conclusions: Leukocyte-related preoperative indicators could predict the prognosis of the patients with TURBT and provided some guidance for clinical workers.

Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue.

Ribosome stalling during translation is detrimental to cellular fitness, but how this is sensed and elicits recycling of ribosomal subunits and quality control of associated mRNA and incomplete nascent chains is poorly understood1,2. Here we uncover Bacillus subtilis MutS2, a member of the conserved MutS family of ATPases that function in DNA mismatch repair3, as an unexpected ribosome-binding protein with an essential function in translational quality control. Cryo-electron microscopy analysis of affinity-purified native complexes shows that MutS2 functions in sensing collisions between stalled and translating ribosomes and suggests how ribosome collisions can serve as platforms to deploy downstream processes: MutS2 has an RNA endonuclease small MutS-related (SMR) domain, as well as an ATPase/clamp domain that is properly positioned to promote ribosomal subunit dissociation, which is a requirement both for ribosome recycling and for initiation of ribosome-associated protein quality control (RQC). Accordingly, MutS2 promotes nascent chain modification with alanine-tail degrons-an early step in RQC-in an ATPase domain-dependent manner. The relevance of these observations is underscored by evidence of strong co-occurrence of MutS2 and RQC genes across bacterial phyla. Overall, the findings demonstrate a deeply conserved role for ribosome collisions in mounting a complex response to the interruption of translation within open reading frames.

Constraint of musculoskeletal tissue and path planning of robot-assisted fracture reduction with collision avoidance.

BACKGROUND: For the robot-assisted fracture reduction, due to the complex fracture musculoskeletal environment, it is necessary to consider the influence of soft tissue traction on preoperative reduction path planning. METHOD: An improved 3D A* algorithm is adopted to plan the fracture reduction path. The distal fragment point clouds are updated to avoid the collision, and the end point coordinates of the muscles are updated to calculate muscular lengths during the path search. RESULTS: 3D reduction path of long-bone fracture is planned, effectively avoiding the fracture fragments collision and ensuring the length of the corresponding muscle is always less than the allowable maximum muscle length after elongation. CONCLUSION: The proposed method can effectively avoid the collision between the distal fragment and the proximal fragment during the fracture reduction, can avoid secondary injury of the muscles around the femoral bone caused by over-distraction, and effectively improve the safety of robot reduction operation.

Bioinformatics analysis of the correlation between m6A RNA methylation regulators and the immune infiltration and prognosis of bladder cancer.

Background: To analyze the effect of N6-methyladenosine (m6A) RNA methylation regulators on the immune infiltration and prognosis of bladder cancer (BC). We explored the related signaling pathways and prognosis-related genes to provide candidate targets for the treatment and prognostic evaluation of BC. Methods: After downloading BC data from The Cancer Genome Atlas (TCGA) database, the expressions of m6A-related genes were obtained. We then performed correlation and sample cluster analysis of the m6A methylation regulator genes as well as difference comparison and survival analysis for the clustered patients using R software. Gene set enrichment analysis (GSEA) was carried out on cluster-grouped samples. Finally, the prognosis-related genes of BC among the m6A methylation regulators were screened. Results: Genomic alterations in the m6A regulators were linked to a poor BC prognosis. HNRNPA2B1, HNRNPC, IGF2BP2, RBM15, YTHDF1, and YTHDF2 were found to be associated with advanced clinical stages of BC. Furthermore, the current study revealed that the levels of the m6A regulators were related to the expression levels and immune infiltration levels of immune regulators [immunosuppressive factors, immunostimulators, and major histocompatibility complex (MHC) molecules] in BC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses suggested that in addition to the relevant immune responses, m6A regulators were involved in the poor prognosis of BC via their participation in blood vessels through regulatory RNA binding, telomeric DNA binding, microRNA (miRNA) binding, negative regulation of messenger RNA (mRNA) processing, negative regulation of DNA biosynthesis, branches of morphogenesis, positive regulation of the Notch receptor target gene transcription, etc. Conclusions: The expression of m6A RNA methylation regulators is closely linked to immune infiltration and prognosis in BC. Thus, it can be utilized as a potential molecular target for the treatment and prognostic assessment of BC.

Low Expression of Keratin17 is Related to Poor Prognosis in Bladder Cancer.

OBJECTIVE: To investigate the association between KRT17 and the prognosis in bladder cancer patients. METHODS: The clinical data of 101 patients with bladder cancer from May 2013 to May 2015 were retrospectively analyzed. At the same time, the expression of KRT17 and its correlation with clinicopathological factors were examined by immunohistochemistry. We search the prognostic value of KRT17 in bladder cancer from the cancer genome map (TCGA) online database. To explore the possible cellular mechanism, gene set enrichment analysis (GSEA) was used. The patients were divided into two groups: high expression of KRT17 and low expression of KRT17. The patients were followed up for 5 years to observe the survival. Kaplan-Meier method and Log rank test were used for univariate survival analysis, and Cox regression analysis was used for multivariate analysis. Finally, a nomogram was constructed on this basis for internal verification. RESULTS: Among the 101 patients, 46 (45.5%) were in the KRT17 low expression group and 55 (54.5%) in the high KRT17 expression group. After 5 years of follow-up, 79 patients survived with a survival rate of 78.2% and 22 patients died with a mortality rate of 21.8%. Kaplan-Meier survival analysis showed that OS and PFS of patients with high expression of KRT17 were significantly higher than those of patients with low expression of KRT17 (p<0.001, p=0.005). Cox multivariate analysis showed that KRT17 expression was an independent risk factor for tumor progression (p=0.019). And tumor size, vascular tumor thrombus, and T stage also affected tumor progression (p<0.05). In the internal validation, the c-index of nomogram was 0.898 (95% CI: 0.854-0.941). CONCLUSION: The decreased expression of KRT17 is associated with poor prognosis in patients with bladder cancer. KRT17 can be used as a novel predictive biomarker to provide a new therapeutic target for bladder cancer patients.

Long Non-coding RNA LINC01094 Promotes the Development of Clear Cell Renal Cell Carcinoma by Upregulating SLC2A3 via MicroRNA-184.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC. Compelling evidence has highlighted the crucial role of long non-coding RNA (lncRNA) in ccRCC. Our current study aims to explore the regulatory mechanism of LINC01094 in the development of ccRCC. Dual-luciferase reporter experiment verified the targeting relationship among miR-184, LINC01094, and SLC2A3. Furthermore, the interaction between LINC01094 and miR-184 was confirmed by RNA immunoprecipitation (RIP) and RNA pull-down. Biological behaviors of ccRCC cells were investigated through cell counting kit-8 (CCK8), scratch test, Transwell, and flow cytometry. The effect of SLC2A3 on the tumorigenicity of nude mice was evaluated in vivo. In ccRCC cells and clinical tissues, LINC01094 and SLC2A3 were highly expressed while miR-184 was lowly expressed. Besides, miR-184 was verified to be a direct target of LINC01094. Silencing LINC01094, up-regulating miR-184, or reducing SLC2A3 inhibited the growth, migration, and invasion of ccRCC cells. Tumor growth was suppressed by silenced LINC01215 via reducing the expression of SLC2A3 via miR-184. Taken together, silencing LINC01094 inhibited SLC2A3 expression by up-regulating miR-184, thereby inhibiting the development of ccRCC.