PHOX2A and PHOX2B are differentially regulated during retinoic acid-driven differentiation of SK-N-BE(2)C neuroblastoma cell line

AbstractPHOX2B and its paralogue gene PHOX2A are two homeodomain proteins in the network regulating the development of autonomic ganglia that have been associated with the pathogenesis of neuroblastoma (NB), because of their over-expression in different NB cell lines and tumour samples. We used the SK-N-BE(2)C cell line to show that all-trans retinoic acid (ATRA), a drug that is widely used to inhibit growth and induce differentiation in NBs, regulates both PHOX2A and PHOX2B expression, albeit by means of different mechanisms: it up-regulates PHOX2A and down-regulates PHOX2B. Both mechanisms act at transcriptional level, but prolonged ATRA treatment selectively degrades the PHOX2A protein, whereas the corresponding mRNA remains up-regulated. Further, we show that PHOX2A is capable of modulating PHOX2B expression, but this mechanism is not involved in the PHOX2B down-regulation induced by retinoic acid. Our findings demonstrate that PHOX2A expression is finely controlled during retinoic acid differentiation and this, together with PHOX2B down-regulation, reinforces the idea that they may be useful biomarkers for NB staging, prognosis and treatment decision making

Decision-making process about prenatal genetic screening: how deeply do moms-to-be want to know from Non-Invasive Prenatal Testing?

Abstract Background Prenatal information may be obtained through invasive diagnostic procedures and non-invasive screening procedures. Several psychological factors are involved in the decision to undergo a non-invasive prenatal testing (NIPT) but little is known about the decision-making strategies involved in choosing a specific level of in-depth NIPT, considering the increased availability and complexity of NIPT options. The main aim of this work is to assess the impact of psychological factors (anxiety about pregnancy, perception of risk in pregnancy, intolerance to uncertainty), and COVID-19 pandemic on the type of NIPT chosen, in terms of the number of conditions that are tested. Methods A self-administered survey evaluated the decision-making process about NIPT. The final sample comprised 191 women (Mage = 35.53; SD = 4.79) who underwent a NIPT from one private Italian genetic company. Based on the test date, the sample of women was divided between “NIPT before COVID-19” and “NIPT during COVID-19”. Results Almost all of the participants reported being aware of the existence of different types of NIPT and more than half reported having been informed by their gynecologist. Results showed no significant association between the period in which women underwent NIPT (before COVID-19 or during COVID-19) and the preferences for more expanded screening panel. Furthermore, regarding psychological variables, results showed a significant difference between perceived risk for the fetus based on the NIPT type groups, revealing that pregnant women who underwent the more expanded panel had a significantly higher level of perceived risk for the fetus than that reported by pregnant women who underwent the basic one. There was no statistically significant difference between the other psychological variables and NIPT type. Conclusions Our findings indicate the paramount role of gynecologist and other health care providers, such as geneticists and psychologists, is to support decision-making process in NIPT, in order to overcome people’s deficits in genetic knowledge, promote awareness about their preferences, and control anxiety related to the unborn child. Decision-support strategies are critical during the onset of prenatal care, according to the advances in prenatal genomics and to parent’s needs