Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer

We determined expression of 83 long non-coding RNAs (lncRNAs) and identified ZFAS1 to be significantly up-regulated in colorectal cancer (CRC) tissue. In cohort of 119 CRC patients we observed that 111 cases displayed at least two-times higher expression of ZFAS1 in CRC compared to paired normal colorectal tissue (P < 0.0001). By use of CRC cell lines (HCT116+/+, HCT116-/- and DLD-1) we showed, that ZFAS1 silencing decreases proliferation through G1-arrest of cell cycle, and also tumorigenicity of CRC cells. We identified Cyclin-dependent kinase 1 (CDK1) as interacting partner of ZFAS1 by pull-down experiment and RNA immunoprecipitation. Further, we have predicted by bioinformatics approach ZFAS1 to sponge miR-590-3p, which was proved to target CDK1. Levels of CDK1 were not affected by ZFAS1 silencing, but cyclin B1 was decreased in both cell lines. We observed significant increase in p53 levels and PARP cleavage in CRC cell lines after ZFAS1 silencing indicating increase in apoptosis. Our data suggest that ZFAS1 may function as oncogene in CRC by two main actions: (i) via destabilization of p53 and through (ii) interaction with CDK1/cyclin B1 complex leading to cell cycle progression and inhibition of apoptosis. However, molecular mechanisms behind these interactions have to be further clarified

Gender determinants of vaccination status in children : evidence from a meta-ethnographic systematic review

Using meta-ethnographic methods, we conducted a systematic review of qualitative research to understand gender-related reasons at individual, family, community and health facility levels why millions of children in low and middle income countries are still not reached by routine vaccination programmes. A systematic search of Medline, Embase, CINAHL, Cochrane Library, ERIC, Anthropological Lit, CSA databases, IBSS, ISI Web of Knowledge, JSTOR, Soc Index and Sociological Abstracts was conducted. Key words were built around the themes of immunization, vaccines, health services, health behaviour, and developing countries. Only papers, which reported on in-depth qualitative data, were retained. Twenty-five qualitative studies, which investigated barriers to routine immunisation, were included in the review. These studies were conducted between 1982 and 2012; eighteen were published after 2000. The studies represent a wide range of low- to middle income countries including some that have well known coverage challenges. We found that women's low social status manifests on every level as a barrier to accessing vaccinations: access to education, income, as well as autonomous decision-making about time and resource allocation were evident barriers. Indirectly, women's lower status made them vulnerable to blame and shame in case of childhood illness, partly reinforcing access problems, but partly increasing women's motivation to use every means to keep their children healthy. Yet in settings where gender discrimination exists most strongly, increasing availability and information may not be enough to reach the under immunised. Programmes must actively be designed to include mitigation measures to facilitate women's access to immunisation services if we hope to improve immunisation coverage. Gender inequality needs to be addressed on structural, community and household levels if the number of unvaccinated children is to substantially decrease

The long non-coding RNA LINC00941 and SPRR5 are novel regulators of human epidermal homeostasis

Several long non-coding RNAs (lncRNAs) act as regulators of cellular homeostasis; however, few of these molecules were functionally characterized in a mature human tissue environment. Here, we report that the lncRNA LINC00941 is a crucial regulator of human epidermal homeostasis. LINC00941 is enriched in progenitor keratinocytes and acts as a repressor of keratinocyte differentiation. Furthermore, LINC00941 represses SPRR5, a previously uncharacterized molecule, which functions as an essential positive regulator of keratinocyte differentiation. Interestingly, 54.8% of genes repressed in SPRR5-deficient epidermal tissue are induced in LINC00941-depleted organotypic epidermis, suggesting a common mode of action for both molecules

Gendered factors influencing vaccination in childhood–overview over the main second-order constructs.

<p>Gendered factors influencing vaccination in childhood–overview over the main second-order constructs.</p

Third-level constructs of gendered factors influencing vaccination in childhood.

<p>Third-level constructs of gendered factors influencing vaccination in childhood.</p

Meta ethnography flowchart.

<p>Meta ethnography flowchart.</p

Definition of 1st, 2nd and 3rd order constructs (adapted from Malpass et al. 2009).

<p>Definition of 1st, 2nd and 3rd order constructs (adapted from Malpass et al. 2009).</p