Summary
The miR-200 microRNA family plays important tumor suppressive roles. The sole Drosophila miR-200 ortholog, miR-8 plays conserved roles in Wingless, Notch and Insulin signaling pathways linked to tumorigenesis, yet homozygous null animals are viable and often appear morphologically normal. We observed that wing tissues mosaic for miR-8 levels by genetic loss or gain of function exhibited patterns of cell death consistent with a role for miR-8 in modulating cell survival in vivo. Here we show that miR-8 levels impact several actin cytoskeletal regulators that can affect cell survival and epithelial organization. We show that loss of miR-8 can confer resistance to apoptosis independent of an epithelial to mesenchymal transition while the persistence of cells expressing high levels of miR-8 in the wing epithelium leads to increased JNK signaling, aberrant expression of extracellular matrix remodeling proteins and disruption of proper wing epithelial organization. Altogether our results suggest that very low as well as very high levels of miR-8 can contribute to hallmarks associated with cancer, suggesting approaches to increase miR-200 microRNAs in cancer treatment should be moderate.
INTRODUCTION:We sought to determine whether the COVID-19 pandemic resulted in an increase in positive urine drug screens (UDSs) in labor and delivery and whether the effect of drug use on neonatal outcomes differed before versus during the pandemic.METHODS:In this retrospective chart review, we identified patients from February 4, 2018, to May 11, 2022, with a completed UDS test and classified them into time periods: pre-COVID-19 and COVID-19. Pearson's χ2 test or Fisher's exact test was used to assess whether the proportion of positive tests and the presence of each drug type differed between the periods. A logistic regression was used to explore the effect of time period and test result on neonatal outcomes.RESULTS:We identified 7,648 UDS results; 3.6% were positive in the pre-COVID-19 period and 1.6% were positive in the COVID-19 period (P<.001). We found higher proportions of benzodiazepine and cannabinoid detection in the pre-COVID-19 period (P=.045 and P=.005, respectively). In the COVID-19 period, we found higher proportions of buprenorphine detection (P=.004). In the COVID-19 period, there was a stronger association between positive UDS results and neonatal intensive care unit (NICU) admission compared to the pre-COVID-19 period (odds ratio [OR] 16.78 [95% CI: 9.9, 28.6], 6.2 [95% CI: 3.8, 10.0], respectively). During the COVID-19 period, drug use was found to be a risk factor for small for gestational age (SGA) (OR 4.1 [95% CI: 2.3, 7.4]).CONCLUSION:We found a decrease in drug use during the COVID-19 pandemic. However, drug use during the pandemic was more strongly associated with NICU admission and was a risk factor for SGA.
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