SLC11A1 promotes kidney renal clear cell carcinoma (KIRC) progression by remodeling the tumor microenvironment.

Kidney renal clear cell carcinoma (KIRC) is a highly immune-infiltrated kidney cancer with the highest mortality rate and the greatest potential for invasion and metastasis. Solute carrier family 11 member1 (SLC11A1) is a phagosomal membrane protein located in monocytes and plays a role in innate immunity, autoimmune diseases, and infection, but its expression and biological role in KIRC is still unknown. In this study, we sought to investigate the potential value of SLC11A1 according to tumor growth and immune response in KIRC. TIMER and UALCAN database was used to analyze the expression feature and prognostic significance of SLC11A1 and its correlation with immune-related biomarkers in KIRC. Proliferation, migration, and invasion were measured using colony formation, EdU, and transwell assays. Role of SLC11A1 on KIRC tumor growth was examined by the xenograft tumor model in vivo. Effects of KIRC cells on macrophage polarization and the proliferation and apoptosis of CD8+ T cells were analyzed using flow cytometry assays. Herein, SLC11A1 was highly expressed in KIRC tissues and cell lines. SLC11A1 downregulation repressed KIRC cell proliferation, migration, invasion, macrophage, and lymphocyte immunity in vitro, as well as hindered tumor growth in vivo. SLC11A1 is significantly correlated with immune cell infiltration and immune-related biomarkers. In KIRC patients, SLC11A1 is highly expressed and positively correlated with the immune-related factors CCL2 and PD-L1. SLC11A1 induced CCL2 and PD-L1 expression, thereby activating the JAK/STAT3 pathway. SLC11A1 deficiency constrained KIRC cell malignant phenotypes and immune response via regulating CCL2 and PD-L1-mediated JAK/STAT3 pathway, providing a promising therapeutic target for KIRC treatment.

Establishment and validation of a nomogram to select patients with metastatic sarcomatoid renal cell carcinoma suitable for cytoreductive radical nephrectomy.

Introduction: Metastatic renal cell carcinoma (mRCC) with sarcomatoid features has a poor prognosis. Cytoreductive radical nephrectomy (CRN) can improve prognosis, but patient selection is unclear. This study aimed to develop a prediction model for selecting patients suitable for CRN. Materials and methods: Patients with a diagnosis of mRCC with sarcomatoid features in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively reviewed. CRN benefit was defined as a survival time longer than the median overall survival (OS) in patients who did not receive CRN. A prediction nomogram was established and validated using the SEER cohort (training and internal validation) and an external validation cohort. Results: Of 900 patients with sarcomatoid mRCC, 608 (67.6%) underwent CRN. OS was longer in the CRN group than in the non-CRN group (8 vs. 6 months, hazard ratio (HR) = 0.767, p = 0.0085). In the matched CRN group, 124 (57.7%) patients survived >6 months after the surgery and were considered to benefit from CRN. Age, T-stage, systematic therapy, metastatic site, and lymph nodes were identified as independent factors influencing OS after CRN, which were included in the prediction nomogram. The monogram performed well on the training set (area under the receiver operating characteristic (AUC) curve = 0.766, 95% confidence interval (CI): 0.687-0.845), internal validation set (AUC = 0.796, 95% CI: 0.684-0.908), and external validation set (AUC = 0.911, 95% CI: 0.831-0.991). Conclusions: A nomogram was constructed and validated with good accuracy for selecting patients with sarcomatoid mRCC suitable for CRN.

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

["Scarless" circumcision technique retaining original appearance].

OBJECTIVE: To explore the safety and effectiveness of the "scarless" circumcision technique (a modified sleeve-style circumcision method) that preserves the original appearance, providing a more suitable surgical option for patients with redundant prepuce. METHODS: Clinical data of patients who underwent "scarless" circumcision at the Eastern Theater Command General Hospital from April 2022 to March 2023 were collected, with patients who underwent conventional circumcision (single-use stapler method) during the same period serving as the control group. The two groups were compared in terms of operation time, postoperative recovery time, incidence of postoperative complications, and patient satisfaction rates after surgery. RESULTS: The operation time for the study group was significantly longer than that of the control group; there was no significant difference in pain scores on the day of surgery between the two groups, but the pain scores on postoperative days 1, 3, and 7 were lower in the study group than in the control group; the postoperative recovery time was significantly shorter in the study group than in the control group; regarding postoperative complications: the control group had higher rates of edema, incision infection, and wound dehiscence than the study group. A satisfaction survey conducted 30 days postoperatively showed higher satisfaction in the study group than in the control group. CONCLUSION: The "scarless" circumcision technique that preserves the original appearance is safe and effective for patients with simple redundant prepuce and is a new surgical method with value for widespread adoption.

[Application of 1470 nm semiconductor laser in the treatment of benign prostatic hyperplasia in ultra-aged patients].

OBJECTIVE: To investigate the clinical effect and safety of transurethral 1470 nm semiconductor laser vaporization and cutting in the treatment of super high age and high risk benign prostatic hyperplasia. METHODS: The clinical data of 38 patients with super-high-risk prostate who underwent transurethral surgery in our hospital from April 2016 to December 2017 were retrospectively analyzed. All patients had obvious progressive dysuria. The diagnosis of benign prostatic hyperplasia was confirmed by urinary color Doppler ultrasound, anal finger examination, PSA, prostate biopsy, etc., and prostate cancer was excluded. Each patient was aged ≥85 years old and combined with one or more types. Senile basic diseases such as diabetes, hypertension, coronary heart disease, emphysema, sequelae of cerebral infarction, etc. The patients were randomly divided into two groups. The observation group was treated with transurethral 1470 nm semiconductor laser vaporization and the control group was treated with transurethral plasma electrotomy. To observe the changes of vital signs, bleeding, duration of surgery, postoperative bladder irrigation time, urinary catheter retention time, and changes of hemoglobin before and after surgery. Surgical safety. The international prostate symptom score (IPSS), quality of life score (QoL), maximum urinary flow rate (Qmax), and post-void residual urine volume (PVR) were evaluated 2 months after surgery and compared with preoperative evaluation to evaluate the surgical outcome. RESULTS: All 38 operations were successfully completed.The vital signs of the patients were stable during the operation. The average operation time of the observation group and the control group was (79.6±24.7 vs 69.5±19.8) min, P>0.05. The hemoglobin decreased by (6.9±3.0) g/L vs (13.2±4.0) g/L， after operation.P<0.05; postoperative bladder irrigation time (14.7±2.8 vs 23.5±5.3)h, P<0.05; average postoperative urinary catheter retention time (3.8±0.4 vs 5.7±0.9)d, P<0.05; average postoperative hospital stay (5.3±1.1 vs 7.2±1.9)d, P<0.05; all patients were followed up for 2 months, IPSS, QoL, Qmax, PVR and other indicators were significantly improved compared with preoperative, no major bleeding, urinary incontinence, cardiopulmonary failure and Significant urinary tract irritation symptoms occur. CONCLUSION: Compared with plasma electric resection, transurethral 1470 nm semiconductor laser treatment of benign prostatic hyperplasia has the advantages of high safety and remarkable effect, especially suitable for patients with high age and high risk.

Exosomal AP000439.2 from clear cell renal cell carcinoma induces M2 macrophage polarization to promote tumor progression through activation of STAT3.

BACKGROUND: Tumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear. METHODS: Macrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation. RESULTS: The ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-ß) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-ß and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo. CONCLUSION: Exosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC. Video Abstract.

[Long-term effect of finasteride on high-risk patients with benign prostatic hyperplasia after implantation of thermo-expandable spiral prostatic stent].

OBJECTIVE: To investigate the long-term effect of finasteride (FS) on high-risk BPH patients after treated by implantation of thermo-expandable spiral prostatic stent (TESPS). METHODS: We retrospectively analyzed the clinical data on 63 cases of BPH treated by implantation of TESPS in our Department of Urology from January 2017 to January 2019. All the patients received oral FS after operation except two cases of stent removal because of infection, 37 for more than 12 months (the long-term FS group) and the other 24 for less than 12 months (the control group). We followed up the patients at 3, 6, 12, 24, 36 and 48 months postoperatively, recorded the incidence of hematuria and infection, IPSS, maximum urinary flow rate (Qmax) and residual urine volume (PVR), and compared them between the two groups of patients. RESULTS: At 48 months after operation, the incidence rates of postoperative hematuria and infection were significantly lower in the long-term FS group than in the control (P < 0.05), but evidently increasing with the prolonging of medication time. The total effectiveness rate was as high as 95.1% at 3 months, but only 63.6% at 48 months, significantly higher, however, in the long-term FS than in the control group (69.2% vs 55.6%, P < 0.05), and the IPSS, Qmax and PVR were also remarkably higher in the former than in the latter group (P < 0.05). CONCLUSION: The long-term effect of TESPS implantation is definite in the treatment of BPH-induced dysuria, and it can be used as a first-choice method for the patients at high risk and unsuitable for surgery. Finasteride has an evident advantage in preventing hematuria and infection after prostatic stent implantation, and long-term medication of finasteride improves long-term outcomes.

Incidence, Clinical Characteristics, and Survival of Collecting Duct Carcinoma of the Kidney: A Population-Based Study.

OBJECTIVE: To investigate the exact age-adjusted incidence (AAI), clinical characteristics, and survival data of collecting duct carcinoma of the kidney (CDCK) recorded in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. METHODS: Patients with CDCK confirmed by microscopic examination from 2004 to 2018 were selected from the SEER database. AAI rates were calculated using SEER*Stat software (version 8.3.9). The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS) rates according to tumor size, tumor stage, and treatment methods, and differences among these variables were assessed by the log-rank test. Cox regression analysis was employed to identify variables independently related to CSS. RESULTS: A total of 286 patients with CDCK were identified from the database. The majority of the patients were white (69.2%), male (67.5%), and married (60.5%), and the median age was 59 years. Most patients with CDCK (74.4%) presented with stages III or IV disease. The diameter of most (59.4%) tumors was less than 7 cm, and the tumors were more commonly found on the left than on the right (55.2% vs. 44.8%). The incidence of CDCK decreased over time. The median CSS time was 17 months. In terms of the treatment modalities used, 83.9% of the patients underwent surgery; 32.9% underwent chemotherapy, and 13.6% underwent radiotherapy. The CSS rates at 1, 2, and 5 years were 57.3%, 43.2%, and 30.7%, respectively. In patients with stage IV CDCK treated with surgery alone, chemotherapy alone, and surgery plus chemotherapy, the median survival time was 5 months, 9 months, and 14 months, respectively (P =0.024). Multivariate Cox regression analysis showed surgery, chemotherapy, stage, regional lymph node metastasis, and distant metastasis were independent prognostic factors for patients with CDCK. CONCLUSIONS: CDCK is an uncommon malignant renal carcinoma, and its incidence is decreasing based on the analysis of current data. CDCK is a high stage, regional lymph-nodes positive, and metastatic disease. Compared with surgery alone or chemotherapy alone, patients with stage IV could gain survival benefit from surgery combined with chemotherapy.

QPCT regulation by CTCF leads to sunitinib resistance in renal cell carcinoma by promoting angiogenesis.

Sunitinib is widely used as a first­line treatment for advanced renal cell carcinoma (RCC). However, a number of patients with RCC who receive sunitinib develop drug resistance; and the biological mechanisms involved in resistance to sunitinib remain unclear. It has previously been suggested that the protein glutaminyl­peptide cyclotransferase (QPCT) is closely related to sunitinib resistance in RCC. Thus, in the present study, in order to further examine the molecular mechanisms responsible for sunitinib resistance in RCC, sunitinib­non­responsive and ­responsive RCC tissue and plasma samples were collected and additional experiments were performed in order to elucidate the molecular mechanisms responsible for sunitinib resistance in RCC. The upstream and downstream regulatory mechanisms of QPCT were also evaluated. On the whole, the data from the present study suggest that QPCT, CCCTC­binding factor (CTCF) and phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit alpha (PIK3CA) may be used as targets for predicting, reversing and treating sunitinib­resistant RCC.

Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells.

Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.

Identification of Immune-Related Cells and Genes in Tumor Microenvironment of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Progression in immunotherapy has provided novel options for the ccRCC treatment. However, the understanding of the ccRCC microenvironment and the potential therapeutic targets in the microenvironment is still unclear. Here, we analyzed the gene expression profile of ccRCC tumors from the Cancer Genome Atlas (TCGA) and calculated the abundance ratios of immune cells for each sample. Then, seven types of immune cells were found to be correlated to overall survival, and 3863 immune-related genes were identified by analyzing differentially expressed genes. We also found that the function of immune-related genes was mainly focused on ligand-receptor binding and signaling pathway transductions. Additionally, we identified 13 hub genes by analyzing the protein-protein interaction network, and seven of them are related to overall survival. Our study not only expands the understanding of fundamental biological features of microenvironment but also provides potential therapeutic targets.

[Spiral thermo-expandable prostatic stent implantation for benign prostatic hyperplasia: Clinical analysis of 26 cases].

OBJECTIVE: To investigate the surgical techniques and clinical effect of Memokath transurethral spiral thermo-expandable prostatic stent (STEPS) implantation in the treatment of BPH. METHODS: From January 2017 to January 2018, 26 BPH patients underwent Memokath transurethral STEPS implantation, 9 under the flexible cystoscope and the other 17 under the rigid cystoscope. The patients were aged 62－91 years old, with a prostate volume of 32－78 ml, postvoid residual urine volume (PVR) of (67.3 ± 11.2) ml, maximum urinary flow rate (Qmax) of (6.3 ± 1.8) ml/s, and IPSS score of 26.7 ± 5.7. Eight of the patients had preoperative urinary retention, of whom, 6 received catheterization and 2 had undergone cystostomy for bladder fistula before STEPS implantation. RESULTS: The operations lasted 15－30 minutes and were successfully completed in 24 cases while stent-shedding occurred in the other 2. Twenty-two of the patients achieved spontaneous urination immediately after surgery and 2 experienced bladder clot embolism. At 3 month after surgery, 24 of the patients showed significant improvement in PVR (ï¼»21.4 ± 7.7ï¼½ ml), Qmax (ï¼»18.3 ± 4.7ï¼½ ml/s) and IPSS (8.3 ± 2.1), and 13 exhibited no statistically significant difference from the baseline in the IIEF-5 score (14.1 ± 1.1 vs 14.3 ± 1.0, P > 0.05). At 12 months, all the patients were found with markedly improved urination but no adverse events except recurrent urinary tract infection in 2 cases. CONCLUSIONS: Memokath STEPS implantation, with its advantages of simple operation, high safety, definite effectiveness, non-influence on sexual function, is a new effective surgical option for the treatment of BPH.

[Clinicopathologic features of testicular seminoma with syncytiotrophoblastic cells: Analysis of 3 cases and review of the literature].

OBJECTIVE: To investigate the clinical and histopathologic features of testicular seminoma with syncytoplasmic trophoblastic components. METHODS: Using light microscopic staining, we analyzed the clinical and histopathologic characteristics, diagnosis, differential diagnosis and prognosis of 3 cases of testicular seminoma with syncytoplasmic trophoblastic components, and reviewed the relevant literature. RESULTS: All the 3 cases were typical seminoma with syncytiotrophoblastic giant cells. Immunohistochemistry showed strong expressions of CD117 OCT-4, SALL4 and PLAP in diffuse tumor cells, and that of hCG in syncytiotrophoblastic cells. Continuous monitoring and consultation exhibited normal levels of serum ß-hCG in all the cases after postoperative chemotherapy. CONCLUSIONS: Testicular seminoma with syncytiotrophoblastic giant cells and increased serum ß-hCG is a rare subtype, which occurs mostly in young people, sensitive to chemotherapy postoperatively and with a relatively good prognosis.

Tooth-Marked Tongue Recognition Using Multiple Instance Learning and CNN Features.

Tooth-marked tongue or crenated tongue can provide valuable diagnostic information for traditional Chinese Medicine doctors. However, tooth-marked tongue recognition is challenging. The characteristics of different tongues are multiform and have a great amount of variations, such as different colors, different shapes, and different types of teeth marks. The regions of teeth mark only appear along the lateral borders. Most existing methods make use of concave regions information to classify the tooth-marked tongue which leads to inconstant performance when the region of teeth mark is not concave. In this paper, we try to solve these problems by proposing a three-stage approach which first makes use of concavity information to propose the suspected regions, then use a convolutional neural network to extract deep features and at last use a multiple-instance classifier to make the final decision. Experimental results demonstrate the effectiveness of the proposed method.

Prognostic Value of a Long Non-coding RNA Signature in Localized Clear Cell Renal Cell Carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) can be used as prognostic biomarkers in many types of cancer. OBJECTIVE: We sought to establish an lncRNA signature to improve postoperative risk stratification for patients with localized clear cell renal cell carcinoma (ccRCC). DESIGN, SETTING, AND PARTICIPANTS: Based on the RNA-seq data of 444 stage I-III ccRCC tumours from The Cancer Genome Atlas project, we built a four-lncRNA-based classifier using the least absolute shrinkage and selection operation (LASSO) Cox regression model in 222 randomly selected samples (training set) and validated the classifier in the remaining 222 samples (internal validation set). We confirmed this classifier in an external validation set of 88 patients with stage I-III ccRCC from a Japan cohort and using quantitative reverse transcription polymerase chain reaction (RT-PCR) in another three independent sets that included 1869 patients from China with stage I-III ccRCC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression, Harrell's concordance index (c-index), and time-dependent receiver operating characteristic curves were used to evaluate the association of the classifier with overall survival, disease-specific survival, and disease-free survival. RESULTS AND LIMITATIONS: Using the LASSO Cox regression model, we built a classifier named RCClnc4 based on four lncRNAs: ENSG00000255774, ENSG00000248323, ENSG00000260911, and ENSG00000231666. In the RNA-seq and RT-PCR data sets, the RCClnc4 signature significantly stratified patients into high-risk versus low-risk groups in terms of clinical outcome across and within subpopulations and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.34 [95% confidence interval {CI}: 1.03-1.75; p=0.028] to 1.89 [95% CI, 1.55-2.31; p<0.001]) after adjusting for clinical and pathologic factors. The RCClnc4 signature achieved a higher accuracy (mean c-index, 0.72) than clinical staging systems such as TNM (mean c-index, 0.62) and the stage, size, grade, and necrosis (SSIGN) score (mean c-index, 0.64), currently reported prognostic signatures and biomarkers for the estimation of survival. When integrated with clinical characteristics, the composite clinical and lncRNA signature showed improved prognostic accuracy in all data sets (TNM + RCClnc4 mean c-index, 0.75; SSIGN + RCClnc4 score mean c-index, 0.75). The RCClnc4 classifier was able to identify a clinically significant number of both high-risk stage I and low-risk stage II-III patients. CONCLUSIONS: The RCClnc4 classifier is a promising and potential prognostic tool in predicting the survival of patients with stage I-III ccRCC. Combining the lncRNA classifier with clinical and pathological parameters allows for accurate risk assessment in guiding clinical management. PATIENT SUMMARY: The RCClnc4 classifier could facilitate patient management and treatment decisions.

Crosstalk between long non-coding RNAs and Wnt/ß-catenin signalling in cancer.

Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the human genome which perform crucial functions in diverse biological processes. The abnormal expression of some lncRNAs has been found in tumorigenesis, development and therapy resistance of cancers. They may act as oncogenes or tumour suppressors and can be used as diagnostic or prognostic markers, prompting their therapeutic potentials in cancer treatments. Studies have indicated that many lncRNAs are involved in the regulation of several signal pathways, including Wnt/ß-catenin signalling pathway, which has been reported to play a significant role in regulating embryogenesis, cell proliferation and controlling tumour biology. Emerging evidences have suggested that lncRNAs can interact with several components of the Wnt/ß-catenin signalling pathway to regulate the expression of Wnt target genes in cancer. Moreover, the expression of lncRNAs can also be influenced by the pathway. Nevertheless, Wnt/ß-catenin signalling pathway-related lncRNAs and their interactions in cancer are not systematically analysed before. Considering these, this review emphasized the associations between lncRNAs and Wnt/ß-catenin signalling pathway in cancer initiation, progression and their therapeutic influence. We also provided an overview on characteristics of lncRNAs and Wnt/ß-catenin signalling pathway and discussed their functions in tumour biology. Finally, targeting lncRNAs or/and molecules associated with the Wnt/ß-catenin signalling pathway may be a feasible therapeutic method in the future.

Long non-coding RNA H19 regulates E2F1 expression by competitively sponging endogenous miR-29a-3p in clear cell renal cell carcinoma.

BACKGROUND: Numerous recent studies indicate that the long non-coding RNAs (lncRNAs) are frequently abnormal expressed and take critical roles in many cancers. Renal cell carcinoma is the secondary malignant tumors in the urinary system and has high mortality and morbidity. Around 80% of RCCs is clear cell renal cell carcinoma (ccRCC) and is characterized by high metastasis and relapse rate. However, the clinical significances of lncRNAs in ccRCC are still unknown. METHODS: The human cancer lncRNA PCR array (Yingbio) was performed to detect the differentially expressed lncRNAs in human ccRCC samples. Real-time PCR (RT-PCR), dual-luciferase assay, RNA binding protein immunoprecipitation (RIP) assay, transwell assay, CCK-8 assay, and western blot were performed to explore the molecular mechanism of lncRNAs in ccRCC cell migration and invasion. RESULTS: In this study, lncRNA-H19 was high expressed and negatively correlated with miR-29a-3p in ccRCC. By bioinformatics software, dual-luciferase reporter and RIP assays, we verified that miR-29a-3p was identified as a direct target of lncRNA-H19. RT-PCR and western blot demonstrated that down-regulated lncRNA-H19 could affect the expression of miR-29a-3p targeting E2F1 with competitively binding miR-29a-3p. Furthermore, transwell assays indicated that lncRNA-H19 knockdown inhibited cells migration and invasion, but this effect was attenuated by co-transfection of lncRNA-H19 siRNA and miR-29a-3p inhibitor. Over expression of E2F1 could rescue lncRNA-H19 siRNA induced suppression on cell migration and invasion in ccRCC cells. CONCLUSIONS: These results show a possible competing endogenous RNAs regulatory network involving lncRNA-H19 regulates E2F1 expression by competitively sponging endogenous miR-29a-3p in ccRCC. This mechanism may contribute to a better understanding of ccRCC pathogenesis, and lncRNA-H19 may be further considered as a potential therapeutic target for ccRCC intervention.

Impact of vascular endothelial growth factor gene-gene and gene-smoking interaction and haplotype combination on bladder cancer risk in Chinese population.

AIMS: To investigate the association of single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) gene polymorphisms, additional gene- gene and gene- smoking interactions with bladder cancer risk. RESULTS: Bladder cancer risk was significantly higher in carriers of the rs699947- A allele within VEGF gene than those with rs699947- CC genotype (CA+ AA versus CC), adjusted OR (95%CI) = 1.70 (1.16-2.31), and higher in carriers of the rs833052- A allele of within VEGF gene than those with rs833052- CC genotype (CA+ AA versus CC), adjusted OR (95%CI) = 1.65 (1.23-2.12). GMDR analysis indicated a potential interaction between rs2010963 and smoking on bladder cancer risk. Current smokers with rs2010963- GC+CC genotype within VEGF gene have the highest bladder cancer risk, compared to never smokers with rs2010963- GG genotype within VEGF gene, OR (95%CI) = 3.25 (1.71-4.83). Haplotype containing the rs2010963- C and rs833052- A alleles were associated with a statistically increased bladder cancer risk, OR (95%CI) = 2.21 (1.12-3.42). MATERIALS AND METHODS: Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association of 6 SNPs within VEGF gene, additional gene- gene and gene- smoking interaction with bladder cancer risk. CONCLUSIONS: We found that the A allele of rs699947 and the A allele of rs833052 within VEGF gene, interaction between rs2010963 and smoking, haplotype containing the rs2010963- C and rs833052- A alleles were all associated with increased bladder cancer risk.

miR-129 predicts prognosis and inhibits cell growth in human prostate carcinoma.

MicroRNAs (miRNAs) are a class of small, well-conserved, non-coding RNAs that are increasingly identified as diagnostic and prognostic biomarkers in a number of cancers. Deregulated miR­129 is closely associated with tumorigenesis and cancer progression. However, the potential role of miR­129 in prostate cancer remains largely elusive. The present study investigated the role of miR­129 as a prognostic biomarker for tumor progression and clinical prognosis in prostate cancer patients. The examined prostate cancer tissues exhibited a significant reduction in miR­129 expression compared with the normal tissues (P=0.013). The expression levels of miR­129 were negatively correlated with histological grade (P<0.001), high preoperative prostate­specific antigen serum levels (P<0.001), pathological stage (P<0.001), high Gleason score (P<0.001), lymph node metastasis (P=0.002), angiolymphatic invasion (P=0.018), and biochemical recurrence (BCR; P=0.001). Use of the Kaplan­Meier analysis demonstrated that low miR­129 expression was closely associated with poorer BCR­free survival. Multivariate survival analysis indicated that miR­129 expression may be an independent prognostic marker for BCR­free survival in prostate cancer patients (P<0.001). Overexpression of miR­129 markedly attenuated prostate cancer cell growth by rescuing cell cycle­regulated protein expression. The present study suggests that miR­129 is downregulated in the cancerous tissues of prostate cancer patients, which was associated with poor BCR­free survival. Thus, it may be considered as a novel independent prognostic biomarker for prostate cancer. In addition, downregulation of miR­129 may serve a critical role in the proliferation of prostate cancer cells.

Long non-coding RNA ATB promotes growth and epithelial-mesenchymal transition and predicts poor prognosis in human prostate carcinoma.

Long non-coding RNAs (lncRNAs) have been identified to be critical mediators in various tumors associated with cancer progression. Long non-coding RNA activated by TGF-ß (lncRNA-ATB) is a stimulator of epithelial-mesenchymal transition (EMT) and serves as a novel prognostic biomarker for hepatocellular carcinoma. However, the biological role and clinical significance of lncRNA-ATB in human prostate cancer have yet to be fully elucidated. The present study was designed to explore the expression of lncRNA-ATB in human prostate cancer patients and the role of lncRNA-ATB in prostate cancer cells. We showed that lncRNA-ATB expression was significantly upregulated in tumor tissues in patients with prostate cancer in comparison with adjacent non-tumor tissues. Further analysis indicted that high lncRNA-ATB expression may be an independent prognostic factor for biochemical recurrence (BCR)-free survival in prostate cancer patients. Overexpression of lncRNA-ATB promoted, and knockdown of lncRNA-ATB inhibited the growth of prostate cancer cells via regulations of cell cycle regulatory protein expression levels. In addition, lncRNA-ATB stimulated epithelial-mesenchymal transition (EMT) associated with ZEB1 and ZNF217 expression levels via ERK and PI3K/AKT signaling pathways. These results indicated that lncRNA-ATB may be considered as a new predictor in the clinical prognosis of patients with prostate cancer. Overexpression of lncRNA-ATB exerts mitogenic and EMT effects of prostate cancer via activation of ERK and PI3K/AKT signaling pathways.