YKL-40 promotes invasion and metastasis of bladder cancer by regulating epithelial mesenchymal transition.

OBJECTIVE: This study aims to explore the relevance between YKL-40 and recurrence and progression of bladder cancer, and determine whether YKL-40 can be used as a potential target in patients with bladder cancer. METHODS: We analyzed the invasion and metastasis ability of BIU-87, UMUC3, J82, T24, 5637 and immortalized human bladder epithelial cells SVHUC1 by Transwell method. The YKL-40 expression levels in cell lines were analyzed by Western blot and qPCR. RESULTS: The increase of YKL-40 level, especially in tumour group, was related to tumour pathological stage and tumour invasion and metastasis. The cell lines with YKL-40 high expression had stronger invasion and metastasis ability. Overexpression of YKL-40 in SVHUC1 with the lowest YKL-40 expression can enhance the invasion and migration of cells. In T24 cells with YKL-40 high expression, transfection of shRNA plasmid targeting YKL-40 can down regulate the invasion and migration. The expression levels of N-cadherin and Vimentin in YKL-40 overexpressed SVHUC1 cells were increased, the E-cadherin expression was decreased, the Twist, Snail and Slug expression levels were increased, but they were opposite in T24 cells with down-regulation of YKL-40 expression. CONCLUSIONS: YKL-40 promoted the migration and invasion of bladder cancer cells by up regulating the EMT gene expression. The YKL-40 expression is closely related to the invasion and migration of bladder cancer.

LncRNA KCNQ1OT1 Promotes Proliferation, Invasion and Metastasis of Prostate Cancer by Regulating miR-211-5p/CHI3L1 Pathway.

BACKGROUND: Bone metastasis after failure of castration therapy is the main reason of death in patients with prostate cancer (PCa). Therefore, full awareness of the metastasis mechanism of PCa and discovery of new therapeutic targets are necessary. Studies showed that lncRNA was involved in the development of cancer. However, its potential role and molecular mechanism in PCa metastasis are still unclear. YKL-40 is an 18 glycosyl hydrolase family protein encoded by CHI3L1, which is involved in the invasion and metastasis of various tumors. A previous study of the authors found that YKL-40 was related to the invasion and metastasis of PCa cells. However, the cause of its abnormal expression in PCa remains unclear. The present study explored the role of lncRNA KCNQ1OT1/miR-211-5p/CHI3L1 regulatory axis in the proliferation, invasion, and metastasis of PCa. METHODS: RT-PCR and Western blot were used to measure the expression profiles of KCNQ1OT1 and YKL. CCK-8 and Transwell assays were used to examine their effects on cell proliferation and migration. Double luciferase reporter assay was used to verify the interactions between miR-211-5p and CHI3L1 3'-UTR. RESULTS: KCNQ1OT1 expression was upregulated in PCa tissues and cells. Downregulating this expression inhibited PCa cell invasion, proliferation, and metastasis. KCNQ1OT1 bound miR-211-5p competitively, and miR-211-5p targeted CHI3L1 3'-UTR. miR-211-5p expression was downregulated, whereas CHI3L1 (YKL-40) expression was upregulated. miR-211-5p levels were negatively correlated with KCNQ1OT1 expression and CHI3L1 mRNA. The decrease in YKL-40 expression in PCa cells induced by the downregulation of KCNQ1OT1 expression could be offset by miR-211-5p inhibitor transfection. CONCLUSION: This study showed that lncRNA KCNQ1OT1, as a ceRNA, upregulated CHI3L1 and promoted PCa progression through competitive binding to miR-211-5p.

PM2.5 inhibits SOD1 expression by up-regulating microRNA-206 and promotes ROS accumulation and disease progression in asthmatic mice.

Bronchial asthma is the most common chronic respiratory disease. Chronic airway inflammation, airflow restriction and airway hyper-responsiveness are its main manifestations. In recent decades, the prevalence and mortality of asthma have been increasing all over the world, which seriously threatens public health. Research suggests that air pollution is associated with the increased incidence of asthma. PM2.5 is one of the most complex pollutants in the atmospheric environment and harmful to human health. It is related to the incidence of asthma. However, the molecular mechanism of PM2.5 in the development of asthma is still unclear. In this study, we established a mouse model of asthma using CRE to observe the effect of PM2.5 on the symptoms of asthmatic mice and its possible molecular mechanism. The results showed that PM2.5 could significantly increase airway resistance and pulmonary inflammation, increase the number of inflammatory cells, eosinophils, macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid in asthmatic mice. Moreover, PM2.5 could reduce the contents of antioxidant enzymes such as CAT, GSH, GSH-Px and T-SOD in lung tissue of mice, and increase the ROS level. PM2.5 can promote the expression of microRNA-206 in lung tissue of mice. miR-206 can target the 3'-UTR of SOD1 to inhibit SOD1 expression, which leads to the increase of ROS level and aggravates pulmonary inflammatory response and asthma symptoms in asthmatic mice. This study found the possible molecular mechanism of PM2.5 aggravating asthma, and miR-206 may be a potential target for asthma treatment.

Triphenylamine-appended cyclometallated iridium(III) complexes: Preparation, photophysical properties and application in biology/luminescence imaging.

Four triphenylamine (TPA)-appended cyclometallated iridium(III) complexes were designed and synthesized. Photophysical properties of these complexes were studied, and density functional theory (DFT) was utilized to analyze the influence of the ancillary ligands (TPA-modified bipyridine) to these complexes. The introduction of TPA units could effectively adjust the lipid solubility of complexes (logP), and endowed complexes with potential bioactivity (anticancer, antibacterial and bactericidal activity), especially in the field of anticancer (the best value of IC50 is 4.34±0.01µM). Interestingly, complexe 4 show some selectivity for cancer cells versus normal cells. Meanwhile, complexes could effectively prevent the metastasis of cancer cells. Complexes can be transported by serum albumin and followed by the static quenching mechanism (Kq: 1013M-1s-1), disturb cell cycle at G0/G1 phase, and induce apoptosis. The favorable fluorescence property confirmed these complexes followed by an energy-dependent cellular uptake mechanism, effectively accumulated in lysosomes (PCC: >0.95) and induced lysosomal damage, and eventually leaded to cell death. Our study demonstrates that these complexes are potential anticancer agents with dual functions, including metastasis inhibition and lysosomal damage.

Half-sandwich iridium(III) complexes with α-picolinic acid frameworks and antitumor applications.

Eight half-sandwich iridiumIII (IrIII) complexes of the general formula [(η5-Cpxbiph)Ir(O^N)Cl] (Cpxbiph is tetramethyl(biphenyl)cyclopentadienyl, and the O^N is α-picolinic acid chelating ligand and its derivatives) were synthesized and characterized. Compared with cis-platin widely used in clinic, target IrIII complexes showed at most five times more potent antitumor activity against A549 cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. IrIII complexes could be transported by serum albumin, bind with DNA, catalyze the oxidation of nicotinamide-adenine dinucleotid (NADH) and induce the production of reactive oxygen species, which confirmed the antitumor mechanism of oxidation. IrIII complexes could enter A549 cells followed by an energy-dependent cellular uptake mechanism, meanwhile, target the mitochondria and lysosomes with the Pearson's colocalization coefficient of 0.33 and 0.74, respectively, lead to the lysosomal destruction and the change of mitochondrial membrane potential (ΔΨm), and eventually induce apoptosis.

YKL-40 promotes the migration and invasion of prostate cancer cells by regulating epithelial mesenchymal transition.

OBJECTIVE: This study aims to observe the expression of YKL-40 in prostate cancer and whether YKL-40 can affect the migration and invasion of tumor cells by regulating epithelial mesenchymal transition. METHODS: We collected 14 cases of prostate cancer tissues and adjacent tissues in this study. The expression levels of YKL-40 in the tissues were analyzed by western blotting and immunohistochemical methods. The expression of YKL-40 in human prostate cancer cell line DU145 and PC3 was detected by fluorescence quantitative PCR and western blotting methods. The expression levels of YKL-40 in different cells were up-regulated or down- regulated by lentivirus to observe the changes of cell migration and invasion. The expression levels of EMT related genes were analyzed by RT-PCR and Western blotting methods. RESULTS: The expression level of YKL-40 in prostate cancer tissues was significantly higher than that in adjacent tissues (P<0.01), and it was higher in DU145 cells than that in PC3 cells (P<0.05). The expression level of YKL-40 was positively correlated with cell migration and invasion. YKL-40 can regulate the expression of EMT related genes (Twist, Snail, Slug, N-cadherin, Vimentin and E-cadherin). CONCLUSIONS: The expression level of YKL-40 was positively correlated with the migration and invasion of prostate cells, it affects cancer metastasis by regulating EMT.

Current status of diagnosis and treatment of bladder cancer in China - Analyses of Chinese Bladder Cancer Consortium database.

OBJECTIVE: To investigate current status of diagnosis and treatment of bladder cancer in China. METHODS: A database was generated by Chinese Bladder Cancer Consortium (CBCC). From January 2007 to December 2012, 14,260 cases from 44 CBCC centers were included. Data of diagnosis, treatment and pathology were collected. RESULTS: The average age was 63.5 year-old and most patients were male (84.3%). The most common histologic types were urothelial carcinoma (91.4%), adenocarcinoma (1.8%), and squamous carcinoma (1.9%). According to 1973 and 2004 WHO grading system, 42.0%, 41.0%, and 17.0% of patients were grade 1, 2, and 3, and 16.0%, 48.7%, and 35.3% of patients were papillary urothelial neoplasms of low malignant potential, low, and high grade, respectively. Non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) were 25.2% and 74.1%, respectively (0.8% not clear). Carcinoma in situ was only 2.4%. Most patients were diagnosed by white-light cystoscopy with biopsy (74.3%). Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%, respectively. Diagnostic transurethral resection (TUR) provided detection rate of 16.9%. Most NMIBCs were treated with TUR (89.2%). After initial TUR, 2.6% accepted second TUR, and 45.7%, 69.9%, and 58.7% accepted immediate, induced, and maintenance chemotherapy instillation, respectively. Most MIBCs were treated with radical cystectomy (RC, 59.7%). Laparoscopic RCs were 35.1%, while open RC 63.4%. Extended and standard pelvic lymph node dissection were 7% and 66%, respectively. Three most common urinary diversions were orthotopic neobladder (44%), ileal conduit (31%), and ureterocutaneostomy (23%). Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18% of T3 and T4 patients accepted adjuvant chemotherapy. CONCLUSION: Disease characteristics are similar to international reports, while differences of diagnosis and treatment exist. This study can provide evidences for revisions of the guideline on bladder cancer in China.

[Expression and clinical significance of nuclear matrix protein 22 and cytokeratin 18 in transitional cell carcinoma of the bladder].

OBJECTIVE: To evaluate the expression and clinical significance of urinary nuclear matrix protein (NMP22) and cytokeratin 18 (CK18) for transitional cell carcinoma of the bladder. METHODS: Urinary NMP22 and CK18 levels of 293 patients with transitional cell carcinoma of the bladder, 400 patients with non-transitional cell carcinoma of the bladder, and 105 bladder benign disease were analysed by enzyme-linked-immunosorbent assay (ELISA). RESULTS: The levels of urinary NMP22 and CK18 in the patients with transitional cell carcinoma of the bladder (M = 17.3 U/ml, M(CK18) = 484.2 U/L) were significantly higher than those in the non-transitional cell carcinoma of the bladder (M = 6.8 U/ml, M(CK18) = 156.0 U/L) and the benign disease group (M(NMP22) = 2.3 U/ml, M(CK18) = 66.6 U/L) (P < 0.001). The sensitivity and specificity of urinary NMP22 and CK18 were 79.2%, 88.6% and 78.2%, 82.9%, respectively, for transitional cell carcinoma of the bladder before any treatment. The joint sensitivity of the two markers was 91.7%. The NMP22 and CK18 levels were significantly lower in the recovered patients after surgical operation (P < 0.01), while in patients with recurrence or metastasis the levels of the markers were significantly higher (P < 0.01). There was a significant relationship between NMP22 and CK18, (r = 0.689, P < 0.01). The levels of urinary nmp22 and CK18 were significantly different among pathological grade G1, G2, G3, and stage Ta, T1, T2, T3 (P < 0.01). CONCLUSION: NMP22 and CK18 are useful tumor marker for diagnosis of transitional cell carcinoma of the bladder and for monitoring the state of illness. The joint use of the two markers can improve the sensitivity of cancer detection. NMP22 and CK18 may become a new class of tumor markers, and to be the basis for development of a new assay with an increased efficacy for the detection and treatment of bladder cancer.