MiR-193b Mediates CEBPD-Induced Cisplatin Sensitization Through Targeting ETS1 and Cyclin D1 in Human Urothelial Carcinoma Cells.

Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) plays multiple roles in tumor progression. Studies have demonstrated that cisplatin (CDDP) induced CEBPD expression and had led to chemotherapeutic drug resistance. However, the underlying molecular mechanisms of CDDP-regulated CEBPD expression and its relevant roles in CDDP responses remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Abnormal miRNAs expression is associated with tumor progression. In current study, a large-scale PCR-based miRNA screening was performed to identify CEBPD-associated miRNAs in urothelial carcinoma cell line NTUB1. Eleven miRNAs were selected with more than twofold changes. MiR-193b-3p, a known tumor suppressor, down-regulated proto-oncogenes Cyclin D1, and ETS1 expression and led to cell cycle arrest, cell invasion, and migration inhibition. The expression of miR-193b-3p was associated with the DNA binding ability of CEBPD in CDDP response. CEBPD knocking-down approach provided a strong evidence of the positive correlation between CEBPD and miR-193b-3p. CDDP-induced CEBPD trans-activated miR-193b-3p expression and it directly targeted the 3'-UTR of Cyclin D1 and ETS1 mRNA, and silenced the protein expression. In addition, miR-193b-3p also inhibited cell migration activity, arrested cell at G1 phase, and sensitized NTUB1 to CDDP treatment. In conclusion, this study indicates that CEBPD exhibits an anti-tumorigenic function through transcriptionally activating miR-193b-3p expression upon CDDP treatment. This study provides a new direction for managing human urothelial carcinoma. J. Cell. Biochem. 118: 1563-1573, 2017. © 2016 Wiley Periodicals, Inc.

Sleep hours and quality before and after baby: Inequalities by gender and partnership.

While prior studies have examined sleep across the lifecourse, few studies have investigated sleep around the birth of a child, one of the most important events to cause sleep deprivation. This study investigates changes in sleep hours and quality, paying attention to differences by gender and partnership status. Using the UK Household Longitudinal Study, we follow approximately 1,000 participants as they transition into parenthood in a three-year window. We use OLS and logistic regression to analyze changes in sleep hours and sleep quality. Results suggest that women's sleep is reduced by an average of 0.7 hours (42 min) on becoming a mother. Whilst before parenthood women sleep more than men, after childbirth women and men sleep similar amounts. Cohabiting men experience a greater reduction in sleep by around 0.5 hours (30 min) than married men, to the level similar to women, suggesting that new cohabiting fathers may experience more sleep disturbances.

Parental Happiness and Social Policy in Asia.

People in East and South Asia widely believe that having children brings fulfillment to an individual's life. However, over the past fifty years, modernisation in Asia has been accompanied by a remarkable drop in birth rates to a level even lower than most western countries. Prior research on western nations has shown that the time demands and financial stresses of parenthood, as well as current inflexible employment practices, contribute to the high cost of parenthood and discount the emotional rewards of having children. This study investigates the happiness of parents and childless individuals in East and South Asia, and whether social policies can improve parental happiness. We use individual-level data in 10 Asian countries from the World Values and the Asian Barometer Surveys, and find no country where parents report significantly greater happiness than non-parents after controlling for relevant sociodemographic differences. Multilevel models show that paid annual leave, paid maternity and parental leave, and flexible working schedules as well as a comprehensive policy index help alleviate the disparity in happiness between parents and non-parents across countries, in particular work flexibility, while family-friendly policies have no noticeable negative effects on non-parents' wellbeing.

Modeling human cancer-related regulatory modules by GA-RNN hybrid algorithms.

BACKGROUND: Modeling cancer-related regulatory modules from gene expression profiling of cancer tissues is expected to contribute to our understanding of cancer biology as well as developments of new diagnose and therapies. Several mathematical models have been used to explore the phenomena of transcriptional regulatory mechanisms in Saccharomyces cerevisiae. However, the contemplating on controlling of feed-forward and feedback loops in transcriptional regulatory mechanisms is not resolved adequately in Saccharomyces cerevisiae, nor is in human cancer cells. RESULTS: In this study, we introduce a Genetic Algorithm-Recurrent Neural Network (GA-RNN) hybrid method for finding feed-forward regulated genes when given some transcription factors to construct cancer-related regulatory modules in human cancer microarray data. This hybrid approach focuses on the construction of various kinds of regulatory modules, that is, Recurrent Neural Network has the capability of controlling feed-forward and feedback loops in regulatory modules and Genetic Algorithms provide the ability of global searching of common regulated genes. This approach unravels new feed-forward connections in regulatory models by modified multi-layer RNN architectures. We also validate our approach by demonstrating that the connections in our cancer-related regulatory modules have been most identified and verified by previously-published biological documents. CONCLUSION: The major contribution provided by this approach is regarding the chain influences upon a set of genes sequentially. In addition, this inverse modeling correctly identifies known oncogenes and their interaction genes in a purely data-driven way.

Family background and contemporary changes in young adults' school-work transitions and family formation in the United States.

The oft-discussed lengthening of the transition into adulthood is unlikely uniform across diverse segments of the population. This study followed youth in the National Longitudinal Survey of Youth 1979 and 1997 cohorts (n = 12,686 and 8,984, respectively) from 16 to 32 years old to investigate this trend in the United States, examining cross-cohort changes in transitions with a focus on differences by family background. Logistic regressions revealed that young adults in the most recent cohort were less likely to have completed schooling, fully entered the labor force, married, or become parents by their 30s than those in the older cohort. The cross-cohort drop in young adults completing schooling was more pronounced among youth from more disadvantaged family backgrounds, the drop in entering the labor force and having children was more pronounced among those from more advantaged backgrounds, and the drop in marriage did not differ by family background.

An integrative approach to identifying cancer chemoresistance-associated pathways.

BACKGROUND: Resistance to chemotherapy severely limits the effectiveness of chemotherapy drugs in treating cancer. Still, the mechanisms and critical pathways that contribute to chemotherapy resistance are relatively unknown. This study elucidates the chemoresistance-associated pathways retrieved from the integrated biological interaction networks and identifies signature genes relevant for chemotherapy resistance. METHODS: An integrated network was constructed by collecting multiple metabolic interactions from public databases and the k-shortest path algorithm was implemented to identify chemoresistant related pathways. The identified pathways were then scored using differential expression values from microarray data in chemosensitive and chemoresistant ovarian and lung cancers. Finally, another pathway database, Reactome, was used to evaluate the significance of genes within each filtered pathway based on topological characteristics. RESULTS: By this method, we discovered pathways specific to chemoresistance. Many of these pathways were consistent with or supported by known involvement in chemotherapy. Experimental results also indicated that integration of pathway structure information with gene differential expression analysis can identify dissimilar modes of gene reactions between chemosensitivity and chemoresistance. Several identified pathways can increase the development of chemotherapeutic resistance and the predicted signature genes are involved in drug resistant during chemotherapy. In particular, we observed that some genes were key factors for joining two or more metabolic pathways and passing down signals, which may be potential key targets for treatment. CONCLUSIONS: This study is expected to identify targets for chemoresistant issues and highlights the interconnectivity of chemoresistant mechanisms. The experimental results not only offer insights into the mode of biological action of drug resistance but also provide information on potential key targets (new biological hypothesis) for further drug-development efforts.

UBE2M-mediated p27(Kip1) degradation in gemcitabine cytotoxicity.

Gemcitabine (2'-deoxy-2', 2'-difluorocytidine; Gem) is a nucleoside anti-metabolite and is commonly used for treating various human cancers including human bladder carcinoma. Gemcitabine not only functions as a suicide nucleoside analog but also inhibits DNA polymerase activity and results in the termination of chain elongation. Using 2-dimensional gel electrophoresis analysis, a Gem-induced protein was identified as UBE2M (a.k.a. UBC12), a NEDD8 conjugation E2 enzyme which contributes to protein degradation. Gem induced UBE2M expression at both RNA and protein levels in several human cancer cell lines. The induction of UBE2M by Gem was accompanied by a reduction in p27(Kip1) protein levels, which could be restored by silencing UBE2M expression with siRNA or by treating cells with the proteasome inhibitor MG132, indicating that UBE2M mediates Gem-induced p27(Kip1) protein degradation. The induction of UBE2M and reduction of p27(Kip1) by Gem were prevented by the PI3K inhibitor LY294002. These results indicate that PI3K activity is necessary for Gem-induced UBE2M expression and that UBE2M facilitates degradation of p27(Kip1). Notably, silencing of UBE2M expression reduced Gem sensitivity in NTUB1 cells, suggesting that UBE2M mediates in part cell sensitivity to Gem, possibly by degradation of p27(Kip1). Analysis of Gem-resistant sub lines also showed that loss of UBE2M and increased p27(Kip1) expression were associated with the acquisition of drug resistance. In conclusion, our results demonstrate a role for UBE2M in mediating cytotoxicity of gemcitabine in human urothelial carcinoma cells while also suggesting a potential function of p27(Kip1) in drug resistance.