miR-10b suppresses cell invasion and metastasis through targeting HOXA3 regulated by FAK/YAP signaling pathway in clear-cell renal cell carcinoma.

BACKGROUND: MicroRNAs have been related to tumor progression in diverse human cancers including clear-cell renal cell carcinoma (ccRCC). Previous study has suggested the important regulation function of miR-10b in ccRCC. However, the direct target of miR-10b in ccRCC and the related molecular mechanisms has not yet been revealed. METHODS: miR-10b and HOXA3 was detected by qRT-PCR. MTT, colony formation assay, wound-healing and transwell assays were performed to detect cell proliferation, colony formation, migration, and invasion abilities in ccRCC. Western blot analyses were performed to evaluate the protein expression of HOXA3, YAP, FAK and MMP-9. Dual luciferase reporter assay was employed to measure potential molecular mechanism of miR-10b in ccRCC. RESULTS: miR-10b was down-regulated in 786-O and A498 cells as compared to renal tubular HK-2 cells. By contrast, HOXA3 and YAP was up-regulated in ccRCC cells and tissues. Functionally, knockdown of YAP inhibited cell proliferation, migration and invasion. Knockdown of FAK downregulated YAP, in turn, resulted in a decrease of HOXA3 expression. Mechanically, miR-10b targets HOXA3 to exert its tumor-suppressive effect on ccRCC in vitro. CONCLUSIONS: These novel data suggest that miR-10b suppresses cell invasion and metastasis through targeting HOXA3, which partially passed through the FAK/YAP signaling pathway.

Microarray expression profiles analysis revealed lncRNA OXCT1-AS1 promoted bladder cancer cell aggressiveness via miR-455-5p/JAK1 signaling.

Bladder cancer (BCa) is one of the most prevalent cancers of the urinary system worldwide. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) perform a vital function in the pathogenesis and progression of BCa. In the current study, we identified a novel lncRNA OXCT1-AS1 and investigated its role and potential mechanisms in BCa. The microarray results showed the expression of lncRNAs, microRNAs, and messenger RNAs between BCa primary tumor tissues and metastatic lymph nodes were significantly different. The quantitative polymerase chain reaction verification was performed to ensure the reliability of the screening results. The Cell Counting Kit 8 and transwell assay were used to assess the tumor cell proliferation and invasion abilities in vitro, respectively. The dual-luciferase activity assay was performed to investigate the potential mechanism of competing endogenous RNA network. lncRNA OXCT1-AS1, which elevated in metastasis lymph node, was significantly upregulated in BCa cell lines compared with SVHUC-1. We demonstrated OXCT1-AS1 inhibited miR-455-5p to decrease its binding to the JAK1 3'-untranslated region, which could upregulate the expression of JAK1 at the protein level, thus promoting BCa proliferation and invasion. Therefore, lncRNA OXCT1-AS1 could act as a potential biomarker and therapeutic target for patients with BCa.

Glucocorticoid-Inducible Kinase 2 Promotes Bladder Cancer Cell Proliferation, Migration and Invasion by Enhancing ß-catenin/c-Myc Signaling Pathway.

Background: Bladder cancer is one of the most common malignancies in urologic system. The glucocorticoid-inducible kinase 2 (SGK2) expression and function were largely unknown in cancers. Current study was aimed to investigate the role of SGK2 in bladder cancer and its potential mechanisms. Methods: SGK2 expression was quantified by western blot (WB) in multiple bladder cancer cell lines (T24, 5637, J82 and UMUC3) compared with normal urothelial cell line (SVHUC). SGK2 knocking down and overexpression model were established by lentivirus transfection. MTT, colony formation, wound healing and transwell assay were used to assess the tumor cell proliferation, migration and invasion abilities, respectively. In addition, molecular function analysis was performed using FunRich software V3. Immunoprecipitation (IP) assay was applied to investigate the interaction between SGK2 and ß-catenin at protein level. TCGA database was retrieved to verify the association between these genes and clinical tumor stage as well as prognosis among bladder cancer patients. Results: SGK2 expression was significantly upregulated in multiple bladder cancer cell lines compared with SVHUC at protein level. Cell proliferation, migration and invasion abilities were significantly decreased after knocking down SGK2 in J82 and UMUC3 cell lines. Inversely, cell aggressive phenotypes were significantly increased after overexpressing SGK2 in T24 cell line. Furthermore, functional analyses of SGK2 based on TCGA database showed that SGK2 related genes were involved in receptor activity, ATP binding, DNA repair protein, trans-membrane receptor activity and lipid binding. In addition, protein interaction analysis identified c-Myc was significantly enriched in SGK2 positively associated genes. The prediction was validated by WB and IP assay that SGK2 could directly bind with ß-catenin at protein level to regulate their downstream gene c-Myc expression in bladder cancer to influence tumor progression. And clinical data generated from TCGA database also identified these downstream genes were significantly associated with tumor stage and survival status of bladder cancer patients. Conclusion: Taken together, our findings suggest SGK2 promotes bladder cancer progression via mediating ß-catenin/c-Myc signaling pathway, which may serve as a potential therapeutic target for bladder cancer patients.

Association of metformin intake with bladder cancer risk and oncologic outcomes in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

BACKGROUND: Recent clinical trials indicated that metformin intake might play a protective role in the incidence and oncologic outcomes of various cancers. However, its protective effect on bladder cancer remains uncertain. METHODS: We performed a meta-analysis to investigate the association between metformin intake and bladder cancer risk as well as oncologic outcomes in diabetes mellitus (DM) patients. A comprehensive literature search was performed using PubMed, Embase, and the Cochrane Central Search Library in December 2017. Hazard ratio (HR) with 95% confidence interval (CI) was pooled. RESULTS: A total of 9 retrospective cohort studies with 1,270,179 patients were included. A meta-analysis revealed that metformin intake was associated with an increased recurrence-free survival (HR = 0.55, 95% confidence interval [CI] = 0.35-0.88; P = .01; I = 64%), improved progression-free survival (HR = 0.70, 95% CI = 0.51-0.96; P = .03; I = 33%), and prolonged cancer-specific survival (HR = 0.57, 95% CI = 0.40-0.81; P = .002; I = 0%). However, results demonstrated that metformin intake was not associated with a decreased incidence of bladder cancer (HR = 0.82, 95% CI = 0.61-1.09; P = .17; I = 85%) or an increased overall survival in bladder cancer patients (HR = 0.83, 95% CI = 0.47-1.44; P = .50; I = 64%). CONCLUSION: The present meta-analysis indicated that metformin intake could improve the prognosis of bladder cancer patients. Further prospective cohort studies and mechanistic studies are still required to determine the precise role of metformin in the initiation and progression of bladder cancer.

Association Between 12 Polymorphisms of VEGF/Hypoxia/Angiogenesis Pathway Genes and Risk of Urogenital Carcinomas: A Meta-Analysis Based on Case-Control Studies.

Objective: Previous studies indicated potential associations between polymorphisms in genes of VEGF/hypoxia/angiogenesis pathway and risk of urogenital carcinomas However, the results were controversial and inconclusive. Here, we conducted an in-depth meta-analysis to investigate the precise associations between polymorphisms in VEGF/hypoxia/angiogenesis related genes and risk of urogenital carcinomas. Methods: We searched PubMed, Web of Science, EMBASE, and Cochrane Library to identify all eligible publications. Pooled odds ratios (ORs) corresponding with the 95% confidence intervals (CIs) were calculated to evaluate their associations. Subgroup analysis was conducted to further ascertain such relationship and investigate sources of heterogeneity. Results: In the end, a total of 96 case-control studies fulfilled the inclusion criteria were enrolled for 12 polymorphisms in 4 VEGF/hypoxia/angiogenesis related genes. The pooled results showed eNOS-rs2070744 polymorphism conferred a significantly increased overall risk of urogenital carcinomas in allele, homozygote, and recessive models, respectively. In addition, eNOS-Intron 4a/b VNTR polymorphism was identified related to an increased risk of urogenital carcinomas in recessive model. And VEGF-rs699947 polymorphism was also identified an increased risk of renal cell carcinoma (RCC) in allelic, heterozygote, dominant, homozygote, and recessive models. Conclusion: To conclude, eNOS-rs2070744 and eNOS-Intron 4a/b VNTR polymorphisms are risk factors for urogenital carcinomas. VEGF-rs699947 polymorphism was also identified as an increased risk factor for renal carcinoma.

Comparative study of the treatment of 20-30 mm renal stones with miniaturized percutaneous nephrolithotomy and flexible ureterorenoscopy in obese patients.

PURPOSE: To evaluate and compare flexible ureteroscopy (f-URS) and mini-percutaneous nephrolithotomy (mPNL) for 20-30 mm renal stones in obese patients regarding efficacy and safety. METHODS: Between May 2011 and June 2017, 254 obese patients who had 20-30 mm kidney stone were consecutively included in the study; 106 patients underwent mPNL and 148 underwent f-URS by the same surgeon. The following parameters were retrospectively assessed: patient and stone characteristics, surgical details, perioperative outcomes, and stone-free rates (SFR). RESULTS: F-URS group was similar to mPNL group in terms of the mean duration of surgery (92.8 ± 26.1 vs 87.4 ± 31.5 min, P = 0.137) and the final SFR (89.1 vs 92.5%, P = 0.381). The f-URS group had significantly shorter postoperative stay (1.0 ± 0.8 vs 4.3 ± 1.7 days, P < 0.001) and lower postoperative complications (11.5 vs 26.4%, P = 0.002). However, the f-URS group had a lower SFR after first session (67.2 vs 87.4%, P < 0.001) and needed more number of procedures (1.5 ± 0.4 vs 1.3 ± 0.4, P < 0.001) than the mPNL group. CONCLUSIONS: MPNL has a higher efficacy (higher SFR after first session and lower number of procedures); however, f-URS offers advantages regarding safety (lower complication rate). Therefore, both options can be offered to obese patients with renal stones from 20 to 30 mm in size. Nevertheless, these results must be confirmed by further prospective randomized trials.

Percutaneous nephrolithotomy in patients with scoliosis: our institutional experience.

It is challenging to treat renal stones in patients with scoliosis. The present study was designed to study the safety and efficacy of minimally invasive percutaneous nephrolithotomy (mPCNL, 18 Fr) and standard tract PCNL (24 Fr) in patients with scoliosis. Twenty cases treated with mPCNL and 18 cases with standard tract PCNL were included in the present study. Laboratory data included preoperative routine complete blood count, serum creatinine, urine bacterial culture, etc. KUB, intravenous urography or CT scanning was done. Fifteen had lumbar and 23 had thoracolumbar scoliosis. Pulmonary function test was performed in all cases. Demographic and clinical details, operative characteristics and complications were studied and compared between two groups retrospectively. The stone burdens of two groups were averagely 754.4 and 816.2 mm(2), respectively (P = 0.194). Pulmonary function test indicated that 18 (47 %) out of 38 patients had decreased function for surgery and anesthesia. The stone clearance rates were 55 and 67 %, respectively, after the first session (P = 0.522). The requirements of auxiliary treatments including second-look PCNL procedure or SWL (shock wave lithotripsy) were not significantly different for both groups. All patients from both groups achieved final stone clearance after auxiliary treatments. Complications of urinary collecting system injury or fever were observed in one and two cases in each group, respectively, (P = 0.548). There were no injuries to neighboring organs or pneumothorax. The requirement of blood transfusion for four cases in mPCNL group and three cases in the standard tract PCNL group, respectively, indicated no significant difference between two groups (P = 0.999). We are able to successfully and safely perform both mPCNL and standard tract PCNL in patients with scoliosis in our hospital. Compared with mPCNL, standard tract PCNL is even more efficient due to its shorter operative time.

Inhibition on calcium oxalate crystallization and repair on injured renal epithelial cells of degraded soybean polysaccharide.

This paper investigated the inhibitory effect of degraded soybean polysaccharide (DPS) on the growth of calcium oxalate (CaOxa) crystals. The results were compared with that of soybean polysaccharide without degradation (SPS). The data showed that DPS exhibited a much higher efficiency to inhibit CaOxa growth and stabilize calcium oxalate dihydrate (COD) compared with SPS. As DPS concentration increased, the soluble Ca(2+) ions significantly increased, the aggregation degree of calcium oxalate monohydrate (COM) crystals decreased, the shape of COD crystals became round and blunt, and the Zeta potential on CaOxa crystal surface reduced. The above results were all conducive for the inhibition of CaOxa crystallization. In addition, DPS displayed a distinct repairing effect on oxidative injured renal epithelial cells in African green monkey (Vero), with enhanced cell viability and extracellular superoxide dismutase activity after repair. The morphologies of the repaired cells and their regulatory capability on CaOxa growth were between the control and injured cells. The results indicated that the risk of stone formation can be reduced by DPS, and that DPS may be a potential green drug to prevent the formation of CaOxa stones.

Neuroendocrine differentiation is involved in chemoresistance induced by EGF in prostate cancer cells.

AIMS: Neuroendocrine (NE) cells were thought to be post-mitotic and non-proliferative. But it was recently reported that NE cells express, and induce surrounding cells to express potent antiapoptotic proteins. We hypothesize that neuroendocrine differentiation (NED), a common phenomenon in prostate cancer, is related to chemoresistance in prostate cancer. MAIN METHODS: Androgen-independent human prostate cancer DU145 and PC-3 cells were exposed to epidermal growth factor (EGF). MTT assays evaluated changes in chemoresistance after EGF treatment, and flow cytometry examined EGF-induced cell cycle changes in DU145 cells. Western blotting, real-time RT-PCR and transmission electron microscopy were utilized to confirm NED. KEY FINDINGS: After stimulation with EGF, DU145 and PC-3 cells exhibited stronger resistance to cisplatin. Flow cytometry showed that EGF stimulation substantially decreased the proportion of DU145 cells in G(1) phase. EGF treatment increased the expression of neuron-specific enolase, a marker of NED induction. SIGNIFICANCE: NED in prostate cancer is involved in the chemoresistance induced by EGF. EGF and/or the EGF receptor may be potential targets for medical intervention in chemo-resistant prostate cancer.

[Mini-percutaneous nephrolithotomy in the treatment of un-hydronephrotic cata-staghorn renal calculi].

OBJECTIVE: To evaluate the surgical techniques and clinical effects of mini-percutaneous nephrolithotomy (mini-PCNL) in the treatment of un-hydronephrotic cata-staghorn renal calculi. METHODS: The clinical data of 46 cases (31 males and 15 females) treated by mini-PCNL were retrospectively analyzed. There were mono-renal calculi in 38 patients (3 patients were the isolated renal calculi) while the other 8 combined opposite side upper urinary tract calculi. The diameter of calculi ranged from 4.2 to 6.4 (mean=5.2) cm. Puncturation was guided by B-type ultrasound. Lithotripsy by air pressure path lithotripter and/or holmium laser was done when the pervium was established. RESULTS: The pervium in the 46 patients was successfully established by one-session puncturation with B-type ultrasonography guidance. The operative time ranged from 140 to 280 (mean=190) min. The amount of blood ranged from 50 to 200 (mean=100) mL and no one needed blood transfusion. Calculus was completely removed in 18 patients (39.1%). Calculi in 10 patients (21.7%) were completely removed among the 20 patients who underwent second-look mini-PCNL. Calculi in 1 of the 3 cases were completely removed by third-look mini-PCNL. Left-over calculi in 17 patients (8 patients after the first time mini-PCNL, 7 patients after second-look, and 2 patients after third-look) were treated by extracorporeal shock-wave lithotripsy (ESWL) and 8 were removed completely. All the 46 patients were followed up for 4 to 48 months. None of them had nephro-hydrops or stenosis. Renal function re-investigation showed that 8 patients recovered and 2 improved in the 10 patients who had azotemia before. Two (5.4%, 2/37) had calculus recurrence in 37 cases which calculi were completely removed before. The size and amount of left-over calculi in 3 patients (33.3%, 3/9) were increasing. CONCLUSION: Mini-PCNL is effective and causes less trauma for un-hydronephrotic cata-staghorn renal calculi. Mini-PCNL combined ESWL may substitute the open operation and is the preferred method for un-hydronephrotic renal cata-staghorn calculi.