RESUMEN
Pumilio (PUM) proteins are members of a highly conserved RNA-binding protein family that posttranscriptionally regulate gene expression in many organisms. However, their roles in the placenta are unclear. In the present study, we report the requirement for the PUM homolog 1 (PUM1) gene in preeclampsia (PE). Immunofluorescence and immunohistochemical data showed that PUM1 was highly expressed in human placental villi from women with PE compared to healthy controls (HCs). Further, PUM1 overexpression repressed, and knockdown enhanced, the invasion and proliferation of trophoblasts. Interestingly, PUM1 knockdown promoted trophoblast invasion in a villous explant culture model, while PUM1 overexpression repressed these effects. Furthermore, lncRNA transcriptome sequencing coupled with RNA immunoprecipitation (RIP) revealed that PUM1 inhibits trophoblast invasion in PE by downregulating the expression of lncRNA HOTAIR. Moreover, PUM1 regulates HOTAIR expression via a posttranscriptional mechanism. Using RNA-protein pull-down and mRNA stability assays, we identified PUM1 as a specific binding partner that decreased the half-life of HOTAIR and lowered the steady-state level of HOTAIR expression, suggesting a novel posttranscriptional regulatory mechanism. Collectively, these findings identified a novel RNA regulatory mechanism, revealing a new pathway governing the regulation of PUM1/HOTAIR in trophoblast invasion in the pathogenesis of PE.
Asunto(s)
Regulación de la Expresión Génica , Preeclampsia/genética , ARN Largo no Codificante/genética , Proteínas de Unión al ARN/genética , Trofoblastos/metabolismo , Línea Celular , Movimiento Celular/genética , Proliferación Celular , Células Cultivadas , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Preeclampsia/metabolismo , Embarazo , Estabilidad del ARNRESUMEN
BACKGROUND: Asthma self-management education combining with behavior therapy is considered to be more effective. Goal setting is a common behavior change technique used to help patients self-manage their symptoms. However, empirical evidence around its effectiveness on asthma management lacks clarity. AIMS: To systematically integrate and appraise the evidence for effectiveness of goal setting interventions on asthma outcomes. METHODS: Databases included CENTRAL, PubMed, EMBASE, CINAHL and Proquest Psychology Database were systematically searched for relevant intervention studies employing goal setting technique as a method in asthma education program for self-management. Characteristic of studies and outcomes in clinical, psychosocial and healthcare utilization outcome were extracted. RESULTS: From a total of 2641 citations, 45 full-text articles were assessed for eligibility and 9 studies met the inclusion criteria. Eight studies were randomized controlled trial and one was before-after study. None studies have a high methodological quality. Goal-setting based intervention appeared to improve symptom control, quality of life and self-efficacy in adult patients with asthma. CONCLUSION: This systematic review highlighted the potential of a goal setting technique in the asthma self-management education. However, due to the limitations of the quality and quantity of the included literature, more rigorous studies are needed. In the future, better effective study protocol combining with goal setting approach and other behavior technique is needed to further investigate.
