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Dishevelled (Dvl) family proteins are overexpressed in nonsmall cell lung cancer (NSCLC), but the correlation between Dvl overexpression and patient prognosis is not clear. The underlying mechanisms of Dvl-1 and Dvl-3 promoting lung cancer cell invasion require further research. We used immunohistochemistry to assess the presence of Dvl-1, Dvl-3, beta-catenin, and p120ctn, and compared their expression to the prognosis in 102 specimens from NSCLC patients. We also examined the effect of Dvl-1 and Dvl-3 on Tcf-dependent transcriptional activity, as well as on the invasiveness in A549 and LTEP-alpha-2 lung cancer cells. The results showed that Dvl-1 correlated to the abnormal expression of beta-catenin, while Dvl-3 correlated to p120ctn. Both Dvl-1 and Dvl-3 were related to the poor prognosis of patient. Dvl-1 overexpression enhanced the Tcf-dependent transcriptional activity and beta-catenin expression significantly. However, Dvl-3 had little effect on the Tcf-dependent transcriptional activity and beta-catenin expression, which was accompanied by p38 and JNK phosphorylation. Furthermore, the invasiveness of Dvl-3-enhanced cells was inhibited by p38 and JNK inhibitors. Exogenous expression of both Dvl-1 and Dvl-3 increased the p120ctn protein expression, while only Dvl-3 upregulated p120ctn mRNA. We conclude that both protein and mRNA of Dvl-1 and Dvl-3 are overexpressed in NSCLC in a manner related to poor prognosis. Dvl-1 may affect the biological behavior of lung cancer cells mainly through beta-catenin (canonical Wnt pathway), while Dvl-3 mainly through p38 and JNK pathway (noncanonical Wnt pathway).

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Purpose: The aim of our study was to validate the sway of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on the metabolism and growth of bladder cancer cells by microRNA-31 (miR-31)/cyclin-dependent kinase 1 (CDK1). Methods:The Gene Expression Omnibus database was used for analyzing the differentially expressed lncRNA and messenger RNA (mRNA) in bladder cancer tissues, with the highly expressed lncRNA PVT1 and mRNA CDK1 screened out. The expression level of PVT1 was detected by quantitative reverse-transcription polymerase chain reaction, cell viability by Cell Counting Kit-8 assay, cell proliferation and scratch by 5-bromo-2′-deoxyuridine assay, cell migration and invasion by transwell assays, the expression level of CDK1 by immunohistochemistry and western blot analysis, transcription factor targeting by dual-luciferase assay, and the effect of PVT1 on bladder cancer growth by nude mice tumor formation experiment.Results: LncRNA PVT1 and mRNA CDK1 had a higher expression in bladder cancer cells than that in neighboring tissues. Activity, proliferation, colony formation, migration, and invasion of bladder cancer cell were noticeably reduced by the PVT1 inhibitor than that of control group. PVT1 and CDK1 have binding sites with miR-31.When miR-31 decreased, CDK1 mRNA and protein levels increased in vivo experiments in nude mice. When PVT1 was downregulated, the tumor size was significantly reduced and tumor proliferation was curbed. Immunohistochemistry showed that the positive rate of CDK1 and Ki-67 decreased and the expression of miR-31 increased after PVT1 was inhibited.Conclusions: LncRNA PVT1 was overexpressed in bladder cancer cells, and it was downregulated miR-31 to enhance CDK1 expression and facilitate bladder cancer cells proliferation, migration, and invasion. K E Y W O R D S bladder cancer, cyclin-dependent kinase 1, long noncoding RNA plasmacytoma variant translocation 1, microRNA-31

As a member of the catenin family, little is known about the clinical significance and possible mechanism of delta-catenin expression in numerous tumours. We examined the expression of delta-catenin by immunohistochemistry in 115 cases of non-small cell lung cancer (NSCLC) (including 65 cases with follow-up records and 50 cases with paired lymph node metastasis lesions). The mRNA and protein expression of delta-catenin was also detected in 30 cases of paired lung cancer tissues and normal lung tissues by RT-PCR and western blotting, respectively. Co-immunoprecipitation was used to examine whether delta-catenin competitively bound to E-cadherin with p120ctn in lung cancer cells or not. The effects of delta-catenin on the activity of small GTPases and the biological behaviour of lung cancer cells were explored by pull-down assay, flow cytometry, MTT, and Matrigel invasive assay. The results showed that the mRNA and protein expression of delta-catenin was increased in lung cancer tissues; the positive expression rate of delta-catenin was significantly increased in adenocarcinoma, stage III-IV, paired lymph node metastasis lesions, and primary tumours with lymph node metastasis (all p < 0.05); and the postoperative survival period of patients with delta-catenin-positive expression was shorter than that of patients with delta-catenin-negative expression (p < 0.05). No competition between delta-catenin and p120ctn for binding to E-cadherin in cytoplasm was found in two lung cancer cell lines. By regulating the activity of small GTPases and changing the cell cycle, delta-catenin could promote the proliferation and invasion of lung cancer cells. We conclude that delta-catenin is an oncoprotein overexpressed in NSCLC and that increased delta-catenin expression is critical for maintenance of the malignant phenotype of lung cancer.

The idea that healthy uterine cavity is sterile is challenged nowadays. It is still debatable whether the bacteria present in the uterine cavity during pregnancy are residents or invaders. To reveal microbiome composition and its characteristics in the womb of pregnant women, 41 decidual tissue samples and 64 amniotic fluid samples were taken from pregnant Chinese women. DNA extraction was followed by pyrosequencing of the hypervariable V4 region of the 16S rDNA gene to characterize womb microbiome. Both types of samples had low diversity microbiome with Enterobacteriaceae being the dominant phylotypes at family level. To characterize the nature of colonization during pregnancy, the presence of endogenous biomass was confirmed by cultivation. Surprisingly, all of the 50 amniotic fluid samples studied were culture-negative, whereas 379 out of 1,832 placenta samples were culture-positive. Our results suggested that womb contained microbiome with low diversity. Culture-based investigation of amniotic fluid and placenta samples confirmed the presence of cultivable microorganisms in the placenta but not in amniotic fluid. Thus it suggests that bacterial colonization does occur during healthy pregnancy.

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