Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to delineate the methylome landscape and characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome. Hypo-methylated regions are enriched in areas with heterochromatin binding markers (H3K9me3, H3K27me3), while hypermethylated regions are enriched in polycomb repressive complex (EZH2/SUZ12) recognizing regions. Altered methylation in promoters, enhancers, and gene bodies, as well as in polycomb repressive complex occupancy and CTCF binding sites are associated with cancerspecific gene dysregulation. Epigenetic-mediated activation of non-canonical WNT/β-catenin/MMP signaling and a YY1/lncRNA ESCCAL-1/ribosomal protein network are uncovered and validated as potential novel ESCC driver alterations. This study advances our understanding of how epigenetic landscapes shape cancer pathogenesis and provides a resource for biomarker and target discovery.

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Groundwater chemistry and its potential health risks are as important as water availability in arid and semiarid regions. This study was conducted to determine the contamination and associated health threats to various populations in a semiarid basin of north China. A total of 78 groundwater samples were collected from the shallow unconfined aquifers. The results showed that the phreatic water was slightly alkaline, hard fresh water with ions in the order of Ca2+ > Na++K+ > Mg2+ and HCO3− > SO42− > Cl−. Four hydrochemical elements, NO3−, F−, Mn and Zn, exceeded the permissible limits. NO3− and F− contaminants may pose health risks to local residents, while the risks of Mn and Zn are negligible. Dermal exposure is safe for all populations, while the oral pathway is not. Minors (i.e., infants and children) are susceptible to both NO3− and F− contaminants, and adults only to NO3−. The susceptibility of various populations is in the order of infants > children > adult males > adult females. Anthropogenic activities are responsible for the elevated levels of NO3−, Zn, Total dissolved solids (TDS), while F− and Mn are from geogenic sources. Thus, differential water supplies, strict control of waste, and rational irrigation practices are encouraged in the basin.

Background Long non‐coding RNAs (lncRNAs) have critical functions within esophageal squamous cell carcinoma (ESCC). However, the function and mechanism underlying ESCC‐associated lncRNA‐1 (ESCCAL‐1) in ESCC tumorigenesis have not been well clarified. Methods ESCCAL‐1, miR‐590 and LRP6 were quantified using qRT‐PCR. Cell viability, migration and invasion abilities were measured using CCK‐8 assay and transwell assays. The protein pression was determined with western blot assay. The xenograft model assays were used to examine the impact of ESCCAL‐1 on tumorigenic effect in vivo. Direct relationships among ESCCAL‐1, miR‐590 and LRP6 were confirmed using dual‐luciferase reporter assays. Results The present work discovered the ESCCAL‐1 up‐regulation within ESCC. Furthermore, ESCCAL‐1 was found to interact with miR‐590 and consequently restrict its expression. Functionally, knocking down ESCCAL‐1 or over‐expressing miR‐590 hindered ESCC cell growth, invasion, and migration in vitro. Moreover, inhibition of miR‐590 could reverse the effect of knockdown of ESCCAL‐1 on cells. Importantly, it was confirmed that LRP6 was miR‐590’s downstream target and LRP6 over‐expression also partly abolished the role of miR‐590 overexpression in ESCC cells. Conclusion We have uncovered a novel regulatory network comprising aberrant interaction of ESCCAL‐1/miR‐590/LRP6 participated in ESCC progression.

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