Amphiregulin Downregulates E-cadherin Expression by Activating YAP/Egr-1/Slug Signaling in SKOV3 Human Ovarian Cancer Cells.

Amphiregulin (AREG) stimulates human epithelial ovarian cancer (EOC) cell invasion by downregulating E-cadherin expression. YAP is a transcriptional cofactor that has been shown to regulate tumorigenesis. This study aimed to examine whether AREG activates YAP in EOC cells and explore the roles of YAP in AREG-induced downregulation of E-cadherin and cell invasion. Analysis of the Cancer Genome Atlas (TCGA) showed that upregulation of AREG and EGFR were associated with poor survival in human EOC. Treatment of SKOV3 human EOC cells with AREG induced the activation of YAP. In addition, AREG downregulated E-cadherin, upregulated Egr-1 and Slug, and stimulated cell invasion. Using gain- and loss-of-function approaches, we showed that YAP was required for the AREG-upregulated Egr-1 and Slug expression. Furthermore, YAP was also involved in AREG-induced downregulation of E-cadherin and cell invasion. This study provides evidence that AREG stimulates human EOC cell invasion by downregulating E-cadherin expression through the YAP/Egr-1/Slug signaling.

HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements.

Hepatocyte nuclear factor 4A (HNF4A/NR2a1), a transcriptional regulator of hepatocyte identity, controls genes that are crucial for liver functions, primarily through binding to enhancers. In mammalian cells, active and primed enhancers are marked by monomethylation of histone 3 (H3) at lysine 4 (K4) (H3K4me1) in a cell type-specific manner. How this modification is established and maintained at enhancers in connection with transcription factors (TFs) remains unknown. Using analysis of genome-wide histone modifications, TF binding, chromatin accessibility and gene expression, we show that HNF4A is essential for an active chromatin state. Using HNF4A loss and gain of function experiments in vivo and in cell lines in vitro, we show that HNF4A affects H3K4me1, H3K27ac and chromatin accessibility, highlighting its contribution to the establishment and maintenance of a transcriptionally permissive epigenetic state. Mechanistically, HNF4A interacts with the mixed-lineage leukaemia 4 (MLL4) complex facilitating recruitment to HNF4A-bound regions. Our findings indicate that HNF4A enriches H3K4me1, H3K27ac and establishes chromatin opening at transcriptional regulatory regions.

Biovalorization of mango byproduct through enzymatic extraction of dietary fiber.

Mango is considered one of the most important tropical fruits worldwide in terms of its consumption and consumer acceptability. Its processing generates huge quantities of mango byproducts, which is often discarded unscrupulously into the environment and, therefore, needs effective waste management practices. The extraction of mango peels' dietary fiber using enzymatic method can be a useful valorization strategy for management of mango by-products. In the present investigation, dietary fiber (soluble and insoluble fraction) was extracted by enzymatic hydrolysis using α-amylase, protease, and amyloglucosidase. Highest yield of dietary fiber (67.5%, w/w) was obtained at 60 °C temperature using recommended enzyme concentrations including α-amylase (40 µL), protease (110 µL), and amyloglucosidase (200 µL) after a treatment time of 60 min. SEM analysis indicated the increased porosity of dietary fiber samples caused due to the hydrolytic effect of enzymes on its surface structure, whereas FTIR analysis confirmed the functional groups present in dietary fiber. The coexistence of crystalline and amorphous nature of polymers present in soluble and insoluble fractions of dietary fiber was assessed by XRD analysis. Further, the analysis of functional properties including WHC, OHC, and SC revealed the suitability of using extracted mango peel's dietary fiber in the food systems.