Clear cell renal carcinoma (ccRCC) is the most common type of kidney cancer. CORO6 functions as an oncogene in various malignancies, including ccRCC, but the mechanisms regulating its expression, particularly at the post-translational level, remain poorly understood. Ubiquitin-specific proteases (USPs), the largest subfamily of deubiquitinases (DUBs), modulate the ubiquitination of target proteins and play crucial roles in numerous biological processes, such as ccRCC tumorigenesis. In this study, we screened USPs that potentially regulate CORO6 stability and identified USP52 as a key regulator that upregulates CORO6 expression. Bioinformatic analysis revealed that USP52 is overexpressed in ccRCC tissues and is negatively associated with patient prognosis. Similarly, USP52 expression was elevated in ccRCC cell lines, and its knockdown led to decreased CORO6 expression in these cells. In vitro experiments demonstrated that USP52 depletion reduced cell viability and proliferation, induced cell cycle arrest, increased apoptosis, and suppressed the migration and invasion of ccRCC cells. USP52 overexpression promotes the malignant phenotype of ccRCC cells. Mechanistically, USP52 interacts with CORO6, significantly decreasing its K48 ubiquitination and preventing its degradation in ccRCC cells. Notably, overexpression of CORO6 in USP52-deficient ccRCC cells effectively restored their malignant behaviors. Furthermore, using a xenograft mouse model of ccRCC, we found that USP52 deficiency impaired tumor growth in vivo, while CORO6 overexpression rescued the growth of USP52-deficient ccRCC cells. Collectively, these findings reveal that USP52 functions as an oncogene in ccRCC by deubiquitinating and stabilizing CORO6.

Fecal microbiota transplantation (FMT) is an emerging therapy for inflammatory bowel disease (IBD), yet its efficacy in patients refractory to conventional treatments and its underlying mechanisms require further elucidation. We studied 37 IBD patients (15 ulcerative colitis [UC], 22 Crohn's disease [CD]) refractory to conventional therapies and 16 healthy donors. FMT monotherapy from a single donor induced week-4 clinical response in 12 UC and 9 biologic-naïve CD patients, with all responders sustaining remission and most achieving endoscopic remission by week 14. Integrated multi-omics revealed FMT restored microbial diversity and profoundly reorganized host-microbiota-metabolite networks. In nine refractory CD patients (7 infliximab [IFX] non-responders, 2 FMT non-responders), IFX-FMT combination led to week-4 response in 6 patients, all of whom attained clinical and endoscopic remission by week 14, with more complete microbial-metabolic restoration than monotherapy. Our findings establish that FMT induces remission in refractory IBD via ecosystem network rewiring, and that IFX-FMT exhibits additive effects, supporting further trials of microbiome-directed adjunctive strategies. IMPORTANCE:This study provides mechanistic and clinical insights into the therapeutic effects of fecal microbiota transplantation (FMT) in inflammatory bowel disease (IBD), particularly when combined with the anti-tumor necrosis factor (anti-TNF) biologic infliximab (IFX). While both FMT and IFX achieve response in approximately 60% of IBD patients, their combined influence on the gut microbial and metabolic landscape in refractory disease has been poorly understood. Here, we demonstrate that FMT monotherapy restores gut microbial diversity and reconfigures host-microbiota-metabolite networks, correlating with clinical and endoscopic remission in patients refractory to conventional treatments. Furthermore, in Crohn's disease patients unresponsive to either therapy alone, combined IFX-FMT induced more complete microbial and metabolic normalization and achieved remission where monotherapy had failed. These findings reveal ecosystem-level network rewiring as a central mechanism of FMT efficacy and establish the additive potential of combining microbiome-targeted and immunomodulatory therapies. This work supports the development of microbiome-informed adjunctive strategies for severe or refractory IBD, highlighting an actionable path toward personalized, mechanism-based treatment regimens. CLINICAL TRIALS:This study is registered with ClinicalTrials.gov as NCT07149441.

Vitexin, a natural flavonoid compound, has shown anti-tumor effects, but its mechanism in Renal cell carcinoma (RCC) remains unclear. Galectin-1, a β-galactoside-binding lectin, promotes tumor progression through metabolic reprogramming. This study examined whether vitexin has antitumor activity against RCC by targeting Galectin-1 and its downstream metabolic pathways. Human RCC cell lines (A498 and ACHN) were treated with vitexin to assess cell viability, apoptosis, cell cycle, migration, and invasion. Galectin-1 expression was manipulated through overexpression and knockdown approaches. Transcriptomic and metabolomic profiling were performed to identify pathway alterations. Glycolytic metabolism was evaluated using ATP measurements, glucose consumption, lactate production assays. The in vivo efficacy was validated using A498 xenograft models in nude mice. Vitexin inhibited RCC cell proliferation, while significantly downregulating Galectin-1 expression. Furthermore, vitexin treatment caused cell cycle arrest, promoted apoptosis, and suppressed colony formation, migration, and invasion. Galectin-1 overexpression rescued vitexin-induced growth inhibition and reduced apoptosis. Transcriptomic analysis revealed that Galectin-1 modulation affected PI3K-AKT pathways, with significant alterations in glycolytic genes (SLC2A1, HK1, HK2, PFKM, PFKP, LDHB). Metabolomic profiling showed Galectin-1-dependent reprogramming of oxidative phosphorylation and energy metabolism. In addition, galectin-1 knockdown impaired glycolytic flux, reduced ATP production, glucose consumption, and lactate secretion. Conversely, Galectin-1 overexpression enhanced these metabolic parameters and activated PI3K/AKT signaling, counteracting vitexin’s metabolic suppression. In vivo, vitexin significantly inhibited tumor growth, downregulated Galectin-1 and PI3K/AKT signaling, reduced cell proliferation, and increased TUNEL-positive apoptotic cells. Vitexin exerts anti-tumor effects in RCC by targeting Galectin-1, which disrupts glycolytic metabolism through PI3K/AKT signaling inhibition. These findings suggest that the vitexin targeting Galectin-1 represents a potential therapeutic strategy for treating RCC.

Abstract Although long noncoding RNAs (lncRNAs) have been implicated in the progression of prostate cancer (PCa), the functional roles of many of these molecules, especially in metastasis, remain poorly understood. To identify novel lncRNAs linked to PCa malignant phenotypes, we analyzed the differences in lncRNA expression between the highly metastatic PCa cell line (PC-3 M-1E8) and the poorly metastatic PCa cell line (PC-3 M-2B4) using transcriptome sequencing. This differential expression was confirmed by RT-qPCR, which showed that the lnc-ALX1-2 gene cluster (including lnc-ALX1-2:5, lnc-ALX1-2:7, lnc-ALX1-2:10) was significantly upregulated in PC-3 M-1E8 cells. Functional studies demonstrated that knockdown of the lnc-ALX1-2 gene cluster suppressed proliferation, migration, and invasion in PC-3 M-1E8 cells, with lnc-ALX1-2:10 showing the most prominent effect. Transcriptome analysis further revealed that lnc-ALX1-2:10 knockdown altered the expression of 194 genes related to both proliferation and migration. RT-qPCR and Western blot validated that lnc-ALX1-2:10 knockdown downregulated pro-tumorigenic factors (CCNE1, PDGFRA, ANGPT4) and EMT markers (N-cadherin, Snail, Vimentin), while upregulating ITGAL and E-cadherin. In vivo, lnc-ALX1-2:10 knockdown obviously decreased tumor volume but had no effect on mouse body weight, and molecular analysis of xenograft tumors confirmed consistent expression changes of key proteins as in vitro. Collectively, our findings identify lnc-ALX1-2:10 as a novel lncRNA that promotes aggressive phenotypes in PCa, highlighting its potential as a therapeutic target for metastatic disease.

Background The increasing epidemiological trend of pediatric urolithiasis over the past three decades has brought it to the forefront of public health attention. An analysis of the disease burden in Brazil, Russia, India, China, and South Africa (BRICS) countries, which share common characteristics such as large population base and limited public health resources, will provide an important reference for global public health policy development. Therefore, this study aimed to investigate the trend of the prevalence of pediatric urolithiasis in BRICS countries during 1990-2021, which in turn will provide more valuable information for them and the world in the prevention and treatment of pediatric urolithiasis.Methods In this study, data were obtained from the Global Burden of Disease (GBD) database. The data were then statistically analyzed using the Joinpoint regression model, AutoRegressive Integrated Moving Average (ARIMA) prediction model, and subgroup analysis to assess trends in the prevalence of pediatric urolithiasis.Result Globally, the prevalence has been increasing every year, with the greatest increase in the 10-14 age group. Encouragingly, the Age-Standardized Prevalence Rate (ASPR) has shown a decreasing trend. The disease burden of pediatric urolithiasis is higher in India and Russia, with the prevalence in India and ASPR in Russia being the highest in the BRICS countries. In South Africa, there is a clear deficit in prevention and treatment in the 0-4 year age group. Additionally, although the burden of pediatric urolithiasis in Brazil is not currently severe, the trend is the fastest deteriorating among the BRICS countries. Finally, China has made significant progress in the prevention and control of pediatric urolithiasis over the past 30 years and is expected to continue this positive trend over the next 15 years.Conclusion This in-depth analysis based on GBD 2021 provides a fresh perspective on the evolving burden of pediatric urolithiasis in BRICS countries over the last three decades. Our research provides valuable insights for policy makers and health care providers through in-depth analysis and scientific evaluation of the prevalence of pediatric urolithiasis using different statistical models. In addition, BRICS countries should develop targeted prevention strategies for at-risk populations and ensure the availability of effective treatments that are tailored to their national contexts while also reflecting global health trends and evidence.

BACKGROUND:In recent years, many studies have illustrated that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor of metastatic castration-resistant prostate cancer (mCRPC), but their conclusions are controversial. The aim of this study was to assess the prognostic value of the NLR in patients with mCRPC treated with docetaxel-based chemotherapy. METHODS:Database searches were conducted in PubMed, EMBASE and the Cochrane Library to retrieve relevant published English-language literature up to 20 February 2023. RevMan 5.4.1 was used to summarize the hazard ratio (HR) and its 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS) with subgroup analysis. Finally, Stata software was adopted for sensitivity analysis, and Egger's test was used to calculate the results of stability to determine whether there was publication bias. RESULTS:A total of 1,983 mCRPC patients from 14 retrospective cohort studies were included in this meta-analysis. The combined results showed that elevated NLR was significantly associated with worse OS (HR = 1.86, 95% CI: 1.55-2.23, P < 0.00001) and PFS (HR = 1.96 (95% CI: 1.52-2.53), P < 0.00001) in patients with mCRPC treated with docetaxel-based therapy. For subgroup analysis of high NLR, studies performed in Asia and cutoff value > 3 were associated with poorer OS, while cutoff values > 3 were associated with poorer PFS. CONCLUSION:Our results suggest that the neutrophil-to-lymphocyte ratio may be a prognostic factor in patients with mCPRC with docetaxel-based chemotherapy.

Background:Urolithiasis is a common disease of the urinary tract, the global prevalence of which is increasing year by year and which, due to its high rate of recurrence and complications, represents a major burden on the quality of life of patients and on the global public health system. As the most populous country in the world, the epidemiology of urolithiasis in China is of great importance. However, the current systematic epidemiological assessment of urolithiasis in China is relatively limited. Therefore, this study used the GBD 2021 database to systematically assess the disease burden of urolithiasis in China to provide a basis for policy formulation. Methods:This study analysed the disease burden of urolithiasis in China between 1992 and 2021, including the number of prevalence cases, prevalence rate and age-standardised prevalence rate, using data from the GBD 2021 database. Joinpoint regression models were used to identify changes in the annual trends of urolithiasis, using annual percent change and average annual percent change for description. Age-period-cohort and Bayesian age-period-cohort models were used to assess time trends in urolithiasis burden and to predict trends over the next 15 years, respectively. Result:The age-standardised prevalence rate of urolithiasis in China has decreased from 96.23 per 100,000 in 1992 to 50.78 per 100,000 in 2021 for males and from 34.44 per 100,000 in 1992 to 22.04 per 100,000 in 2021 for females. While the number of men with the disease has declined slightly, the number of women with the disease has increased. The Joinpoint regression model showed that the age-standardised prevalence rate showed a consistent downward trend in both males and females, and that the periods in which the decline was most pronounced were very similar. The age-period-cohort model also confirmed that the period and cohort effects of urolithiasis showed a decreasing trend from year to year. In addition, the age effect suggested that the risk of urolithiasis tended to increase and then decrease with age, and that the risk was highest in the 55-59 age group. Finally, the Bayesian age-period-cohort prediction model showed that the age-standardised prevalence rate of urolithiasis in both males and females would show a slowly increasing trend over the next 15 years. Conclusion:In this study, we analysed the trend of the disease burden of urolithiasis in China during 1992-2021 by GBD 2021. The results showed that the burden of urolithiasis was significantly higher in males than in females. Furthermore, although the burden of urolithiasis has gradually improved in both men and women over the past 30 years, the BAPC prediction model suggests that the burden of urolithiasis is likely to increase in the next 15 years in both sexes. Therefore, prevention, early screening and treatment of urolithiasis in high-risk groups need to be strengthened to respond effectively to a possible future increase in burden.

Background:Over the past three decades, male infertility has become a significant burden on global public health. As an international organization with nearly half of the world's population, BRICS plays a crucial role in global health. This study investigates the trend of male infertility burden in BRICS countries from 1990 to 2021, providing valuable information for prevention and treatment strategies. Methods:Data on male infertility in BRICS countries were obtained from the Global Burden of Disease database. Joinpoint regression, decomposition analysis, and prediction models were applied to analyze the data and assess the disease burden trends. Results:The global prevalence of male infertility has worsened significantly between 1990 and 2021, with projections indicating this trend will continue for the next 15 years. While this global trend is based on data from a range of countries, the results of this study specifically focus on the BRICS countries. In these countries, while China and the Russian Federation have had high prevalence rates, improvements were observed over the past 30 years. India and Brazil, though unable to control male infertility in this period, have managed to halt its worsening in recent years. South Africa experienced substantial fluctuations from 2001 to 2015, with further significant changes projected in the next 15 years. Conclusion:This study provides valuable insights into the evolving burden of male infertility in BRICS countries. It underscores the importance of targeted prevention and treatment strategies for these countries based on national and global trends.

BackgroundOsteomyelitis is characterized by an inflammatory process initiated by microorganisms, leading to infection and subsequent degradation of bone tissue. Several studies have indicated a potential link between gut microbiota and the occurrence of osteomyelitis. Utilizing the benefits of Mendelian randomization, which mitigates issues of confounding and reverse causation, we employed this approach to ascertain the presence of a causal connection between gut microbiota and osteomyelitis. Additionally, we aimed to pinpoint gut microbiota that could potentially exert substantial influence.MethodsWe performed a rigorous screening of single nucleotide polymorphisms in GWAS summary statistics for gut microbiota and osteomyelitis. The 2,542 instrumental variables obtained after screening were subjected to MR analyses, including inverse variance weighting, weighted median, weighted mode, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier test. We then validated the reliability of the results by performing sensitivity analyses on the MR of 196 well-defined gut microbiota.ResultWe established a causal relationship between gut microbiota and osteomyelitis through MR analysis. Additionally, we identified a taxon of significant importance and six taxons with nominal significance. Specifically, the family Bacteroidales S24.7 group exhibited an association with a diminished risk of osteomyelitis development. Conversely, the class Bacilli, class Bacteroidia, order Bacteroidales, order Lactobacillales, family Streptococcaceae, and genus Coprococcus3 displayed an increased risk of developing osteomyelitis. The MR outcomes for these seven taxa remained stable throughout a series of sensitivity analyses.ConclusionThis study demonstrated a causal relationship between gut microbiota and osteomyelitis by Mendelian randomization. We hope that this study will provide a new direction for the treatment of osteomyelitis, which has a paucity of therapeutic options.

Erectile dysfunction ranks among the prevalent sexual disorders in men. Several studies have indicated a potential link between gut microbiota and erectile dysfunction. To validate this potential association, we were to screen statistical data from genome-wide association studies of gut microbiota and erectile dysfunction. p values of less than 1 × 10−5 were set as the threshold for screening instrumental variables that were strongly associated with gut microbiota. At the same time, in order to obtain more convincing findings, we further excluded instrumental variables with possible chain imbalance, instrumental variables with the presence of palindromes, instrumental variables with F-statistics less than 10, and instrumental variables associated with risk factors for erectile dysfunction. Five methods including inverse-variance weighted method, weighted median method, weighted mode, Mendelian randomization egger method and Mendelian randomization pleiotropy residual sum and outlier test were then used to analyse the 2591 instrumental variables obtained from the screening. We identified correlations between six gut microbiota and the risk of erectile dysfunction. The genus Ruminococcaceae UCG-013 exhibited an inverse association with the risk of developing erectile dysfunction (0.79 (0.65–0.97), P = 0.0214). Conversely, the genus Tyzzerella3 (1.13 (1.02–1.26), P = 0.0225), genus Erysipelotrichaceae UCG-003 (1.18 (1.01–1.38), P = 0.0412), genus LachnospiraceaeNC2004group (1.19 (1.03–1.37), P = 0.0191), genus Oscillibacter (1.23 (1.08–1.41), P = 0.0022), and family Lachnospiraceae (1.26 (1.05–1.52), P = 0.0123) demonstrated positive associations with an increased risk of erectile dysfunction. These sensitivity analyses of the gut microbiota were consistent. This study demonstrated a possible causal relationship between gut microbiota and erectile dysfunction risk through Mendelian randomization analysis, providing new potential possibilities for the prevention and treatment of erectile dysfunction.

Abstract Objectives Bladder cancer (BCa) is one of the most frequently diagnosed cancers of the urinary tract and has a high mortality. The M2 splice isoform of pyruvate kinase (PKM2) is a key regulator of the Warburg effect in cancer cells. This study aimed to evaluate metabolic alterations and biological behaviours after knocking down PKM2. Methods In this study, 36 pairs of BCa tissues and adjacent normal tissues were collected to analyse the expression level of PKM2 and to explore the relationship between PKM2 level and tumour and patient status. After PKM2 knockdown in T24 cells, cell survival, migration, invasion, glucose uptake, lactate production, and apoptosis were detected. The tumour-forming ability of PKM2-reducing T24 cells was examined in vivo. Results The results showed that PKM2 expression correlates with BCa stage and grade. PKM2 knockdown decreases glucose consumption and lactate production and suppresses cell proliferation, migration, and invasion while increasing reactive oxygen species levels and apoptosis in T24 BCa cells in vitro. In nude mouse models, PKM2 knockdown reduced xenograft and orthotopic tumour size. Moreover, PKM2 knockdown decreased vimentin and fibronectin expression and increased E-cadherin expression. Analysis of high-throughput sequencing data revealed that PKM2 may also be associated with biological processes and diseases. Conclusions Overall, these results indicate that PKM2 may be a therapeutic target for BCa patients.

Understanding the molecular mechanism of clear cell renal cell carcinoma (ccRCC) is essential for predicting the prognosis and developing new targeted therapies. Our study is to identify hub genes related to ccRCC and to further analyze its prognostic significance. The ccRCC gene expression profiles of GSE46699 from the Gene Expression Omnibus (GEO) database and datasets from the Cancer Genome Atlas Database The Cancer Genome Atlas were used for the Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis. We screened out 397 overlapping genes from the four sets of results, and then performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways. In addition, the protein-protein interaction (PPI) network of 397 overlapping genes was mapped using the STRING database. We identified ten hub genes (KNG1, TIMP1, ALB, C3, GPC3, VCAN, P4HB, CHGB, LGALS1, EGF) using the CytoHubba plugin of Cytoscape based on the Maximal Clique Centrality (MCC) score. According to Kaplan-Meier survival analysis, higher expression of LGALS1 and TIMP1 was related to poorer overall survival (OS) in patients with ccRCC. Univariate and multivariate Cox proportional hazard analysis showed that the expression of LGALS1 was an independent risk factor for poor prognosis. Moreover, the higher the clinical grade and stage of ccRCC, the higher the expression of LGALS1. LGALS1 may play an important role in developing ccRCC and may be potential a biomarker for prognosis and treatment targets.

汇报1例肾血管平滑肌脂肪瘤(renal angiomyolipoma,RAML)伴静脉瘤栓年轻女性患者的诊断与治疗,并复习文献,重点探讨预防瘤栓脱落方法及保留肾单位手术的可行性.该患者尝试行机器人辅助腹腔镜下静脉取栓术+肾部分切除术,因取净瘤栓困难,血流阻断时间过长改行肾切除术.病理证实为RAML伴静脉瘤栓.RAML合并静脉瘤栓具有潜在的瘤栓脱落、肺动脉栓塞等高死亡风险.术前腔静脉滤器置入联合肾动脉栓塞可以尽可能地降低瘤栓脱落风险.保留肾单位治疗的手术方式具有挑战性,但是已经有成功案例,值得尝试.

Background Recent studies have suggested a possible association between gut microbiota and bipolar disorder (BD). However, observational studies are limited and there are variations between the gut microbiota taxa found in different studies. Therefore, we aimed to explore whether there is a causal relationship between gut microbiota and bipolar disorder at the genetic level and to reveal trends in the effect of influential gut microbiota on the development of bipolar disorder. Methods We conducted a Mendelian randomisation (MR) study of summary statistics from a genome-wide association study (GWAS) of gut microbiota and bipolar disorder. Inverse variance weighting (IVW) was used as the primary method of statistical analysis, while results from the MR-Egger method, weighted median, weighted mode, and MR multiplicity residuals and outliers (MR-PRESSO) tests were used for additional validation.Cochrane’s Q test, MR-Egger intercept test, and MR-PRESSO global test were used to test MR results for stability and reliability. Result We identified 13 gut microbial taxa causally associated with bipolar disorder. Betaproteobacteria, Acidaminococcaceae, Eubacterium xylanophilum group, Butyricimonas, Peptococcus, Prevotella 7, Roseburia, Terrisporobacter, Burkholderiales and Desulfovibrionales increased the risk of BD, whereas Candidatus Soleaferrea, Ruminiclostridium 5 and Victivallis decreased the risk of BD. The results of the MR analysis were shown to be reliable in the sensitivity analysis. Conclusion With the MR study, we analysed the causal relationship between 196 gut microbial taxa and bipolar disorder and also identified gut microbiota associated with the risk of developing bipolar disorder. Our findings provide new biomarkers and potential therapeutic targets for the prevention and treatment of BD.

Background: Bladder cancer (BC) is the 10th most common malignancy worldwide. The high recurrence rates of BC lead to significant treatment challenges. With the development of molecular biology techniques, research has shown that gene abnormalities are closely related to the occurrence and development of BC. This study analyzed the detection results of gene mutations in the tissue samples of BC patients and explored the relationship between fibroblast growth factor receptor 3 (FGFR3) and the prognosis and recurrence of BC. Methods: This study examined 82 Chinese patients with BC. Of these patients, 34 underwent radical cystectomy (RC), and 48 underwent transurethral resection with intravesical instillation. In addition, multigene panel targeted next-generation sequencing (NGS) of the samples was performed. Results: The mutational spectra revealed that C > T was the most common base substitution. Single nucleotide polymorphism (SNP) and deletion (DEL) were the common variant types in our cohort. The top 10 mutant genes were ROS1 (37%), PIK3CA (35%), FGFR3 (34%), BRAF (34%), ERBB2 (32%), ALK (27%), RET (27%), NTRK1 (24%), MET (23%), and EGFR (18%). FGFR3 mutations were detected more frequently in non-muscle-invasive bladder cancer (stages 0a, I) patients than in muscle-invasive bladder cancer (stage II, III, and IV) patients. The top 3 altered types of FGFR3 were p.Ser249Cys, p.Tyr375Cys, and p.Arg248Cys. Conclusions: This study examined the mutated types and frequency of FGFR3 and the prognosis of Chinese BC patients with FGFR mutations. We hope that our findings will enable clinical individualization strategies for BC patients to be optimized.

Long non-coding RNAs (lncRNAs) have been implicated in the progression and development of many types of cancer by interacting with RNA, DNA and proteins, including DLEU7-AS1. However, the function of DLEU7-AS1 in renal cell cancer (RCC) remains unclear. In this study, two in silico prediction algorithms were used to discover the potential target of miR-26a-5p, which was determined to be a tumor suppressor gene, possibly DLEU7-AS1, through the downregulation of coronin-3 in RCC. Thus, we hypothesized that DLEU7-AS1 promotes RCC by silencing the miR-26a-5p/coronin-3 axis. To test our hypothesis, we confirmed that DLEU7-AS1 directly targets miR-26a-5p using the pmirGLO dual-luciferase reporter assay. Next, we observed that DLEU7-AS1 expression was markedly upregulated in RCC samples and inversely correlated with clinical prognosis and miR-26a-5p levels. Knockdown of DLEU7-AS1 significantly suppressed the growth and metastasis of RCC cells in vitro and attenuated tumor growth in vivo. Interestingly, exogenous expression of coronin-3 or miR-26a-5p inhibitor treatment almost completely rescued the DLEU7-AS1 knockdown-induced inhibitory effects on cell proliferation, migration and invasion. In conclusion, our data demonstrate that DLEU7-AS1 is an oncogene in RCC capable of regulating the growth and metastasis of RCC by silencing the miR-26a-5p/coronin-3 axis, suggesting that DLEU7-AS1 can be employed as a potential therapeutic target and prognostic biomarker for RCC.

Long non-coding RNAs are a diverse catalog of RNAs that have been implicated in various aspects of tumorigenesis. Emerging evidence indicates that they play crucial roles in tumor growth, disease progression, and drug resistance. However, the clinical significance of lncRNAs in tumor behavior prediction and disease prognosis as well as the underlying mechanism in renal cell carcinoma (RCC) remains elusive. By analyzing the gene expression profiles of 539 RCC patients from the TCGA cohort and 40 RCC patients from an independent cohort, we identified FAM13A-AS1, a poorly studied lncRNA, upregulated in RCC patients. Knockdown experiments revealed that FAM13A-AS1 promotes cell proliferation, migration, and invasion by interacting with miR-141-3p. FAM13A-AS1 regulates the expression of NEK6 by decoying miR-141-3p. In addition, there was a strong positive correlation between the expression of FAM13A-AS1 and NEK6 in RCC patients. In summary, our results demonstrate the oncogenic role of FAM13A-AS1 in RCC and suggest that it promotes tumorigenesis by upregulating the expression of NEK6 by competitively binding to miR-141-3p.

Renal cell carcinoma (RCC) constitutes the most lethal type of genitourinary cancer. Understanding of RCC tumor biology helps to identify novel targets and develop directed treatments for patients with this type of cancer. Analysis from both The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset and our RCC samples demonstrated that the expression level of CORO6 was significantly higher in RCC patients than in normal kidney tissues, and its level was highly associated with tumor stage and grade. Importantly, CORO6 expression level was an independent predictor of tumor metastasis and overall survival in RCC patients. Our cell line data also confirmed that CORO6 knockdown could suppress RCC cell growth as well as cell migration and invasion. The depletion of CORO6 led to cell cycle arrest at the G0/G1 phase and caused cell apoptosis. Further, mechanistic dissection showed that CORO6 mediated RCC cell growth, and cell invasion relied on WNT signaling. Moreover, the in vivo data suggested that CORO6 knockdown indeed suppressed RCC tumor growth. Overall, our study defines the oncogenic role of CORO6 in RCC progression and provides a rationale for developing CORO6-targeted therapies for improved treatment of RCC patients.

目的 探讨HMGN5基因敲除对人膀胱上皮癌细胞顺铂化疗敏感性的影响.方法 采用不同浓度CDDP(0、1、2、4,8、16 μg/ml)处理人UBC细胞系,采用Western blot、菌落形成、细胞侵袭、细胞凋亡及Hoechst 33342染色法评价HMGN55蛋白敲除对UBC细胞CDDP敏感性的影响,同时分析HMGN5基因参与到UBC细胞CDDP治疗环节可能分子机制.结果 UBC细胞株5637、t24及UM-UC-3中HMGN5蛋白表达,其中5637细胞系HMGN5蛋白水平最高,而UM-UC-3细胞中最低(P＜0.05);5637细胞系对CDDP敏感性显著低于其他两种(P＜0.05),且UM-UC-3细胞系敏感性最高;UBC细胞系HMGN5敲除后P-Akt表达显著下降(P＜0.05);CDDP处理后P-Akt活性亦随之降低(P＜0.05);CDDP处理还可下调VEGF-C和SLUG表达,上调E-Cad表达(P ＜0.05);5637细胞HMGN5基因敲除后早期凋亡率显著提高,而加入IGF-1可逆转这一过程(P＜0.05);与阴性对照组和IGF-1治疗组相比,HMGN5敲除组凋亡核百分比显著升高(P＜0.05);与对照组相比,HMGN5基因敲除显著下调P-AKT和VEGF-C表达,上调E-Cad、细胞色素C、裂解半胱天冬酶-3、裂解PARP表达(P＜0.05);而添加IGF-1可逆转以上蛋白质表达变化(P＜0.05).结论 HMGN5可能是顺铂治疗潜在靶点,抑制HMGN5基因有助于增加UBC细胞化疗敏感性,这一作用主要通过干扰PI3K/Akt信号通路实现.

Coronin-3 (coronin-1C), a homotrimer F-actin-binding protein, has been reported to be important for metastasis in several types of cancers such as lung cancer, gastric cancer, and breast cancer. Here, we present an investigation of the expression and function of coronin-3 in renal cell cancer for the first time. We also confirmed that miR-26 directly targets coronin-3 and down-regulates its expression by western blot assay and dual-luciferase reporter system. The results of MTT and colony formation assay showed that miR-26 suppressed cell proliferation. Wound healing and transwell assay revealed that miR-26 inhibited migration and invasion of renal cancer cell. Moreover, overexpression of coronin-3 could reverse the miR-26-induced inhibition in cell growth and metastasis. Thus, our study suggests that coronin-3 should serve as a potential therapeutic target in renal cell cancer and provide a candidate for miRNA therapy.