Genome-Wide Identification and Analysis of Enhancer-Regulated microRNAs Across 31 Human Cancers.

Enhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner, and dysregulation of target genes could lead to various diseases, such as cancer. Recent studies have shown that enhancers can regulate microRNAs (miRNAs) and participate in their biological synthesis. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer-miRNA interactions and 1,280 distal enhancer-miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited a significant cancer type-specific feature trend at the tissue level rather than at the single-cell level, and there was a noteworthy positive correlation between the expression of the miRNA and the number of enhancers regulating the same miRNA in most cancers. Furthermore, we found that there was a high correlation between the formation of enhancer-miRNA pairs and the expression of enhancer RNAs (eRNAs) whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, guanine-cytosine (GC) content, and histone modification signatures. Notably, GC content, H3K4me1, and H3K36me3 were present differently between distal and proximal regulation, suggesting that they might participate in chromosome looping of enhancer-miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391-1186507 ∼ miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on the enhancer affected the expression of the TNFRSF18 gene as a tumor suppressor.

Characterization of PM2.5-bound phthalic acid esters (PAEs) at regional background site in northern China: Long-range transport and risk assessment.

Eleven major phthalic acid esters (PAEs) congeners were analyzed for PM2.5 samples collected at Mount Tai, a high elevation mountain site in northern China from June to August 2015. The results showed that the average concentration of PAEs in PM2.5 was 19.48ngm-3, and bis(2-Ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and diisobutyl phthalate (DIBP) were the predominant species in particle-phase, whereas diethyl phthalate (DEP) and dimethyl phthalate (DMP) were the prevailing PAEs in gas-phase. PAE concentrations decreased at the beginning of cloud/fog events, while they increased after the cloud/fog events since the liquid-phase PAEs could be absorbed by solid-phase PAEs. Potential source contribution function (PSCF) analysis and principal component analysis (PCA) revealed that the highest PSCF value of air masses were mainly sourced from southwest of Mount Tai and multiple sources contributed to PAEs. A Monte Carlo simulation was applied to estimate the incremental lifetime cancer risks (ILCR) from inhalation exposure on the basis of DEHP concentrations. The estimated values of ILCR for the general population were lower than the U.S. Environmental Protection Agency threshold, which is 10-6. However, since the local population was exposed to various local emission sources, the actual health risk is undervalued.

Analysis on the interaction domain of VirG and apyrase by pull-down assay.

VirG is outer membrane protein of Shigella and affects the spread of Shigella. Recently it has been reported that apyrase influences the location of VirG, although the underlying mechanism remains poorly understood. The site of interaction between apyrase and VirG is the focus of our research. First we constructed recombinant plasmid pHIS-phoN2 and pS-(v1-1102, v53-758, v759-1102, v53-319, v320-507, v507-758) by denaturation-renaturation, the phoN2:kan mutant of Shigella flexneri 5a M90T by a modified version of the lambda red recombination protocol originally described by Datsenko and Wanner and the complemented strain M90TΔphoN2/pET24a(PhisphoN2). Second, the recombinant plasmid pHIS-phoN2 and the pS-(v1-1102, v53-758, v759-1102, v53-319, v320-507, v507-758) were transformed into E. coli BL21 (DE3) and induced to express the fusion proteins. Third, the fusion proteins were purified and the interaction of VirG and apyrase was identified by pull-down. Fourth, VirG was divided and the interaction site of apyrase and VirG was determined. Finally, how apyrase affects the function of VirG was analyzed by immunofluorescence. Accordingly, the results provided the data supporting the fact that apyrase combines with the α-domain of VirG to influence the function of VirG.