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Enhancers are critical for regulating tissue-specific gene expression, and genetic variants within enhancer regions have been suggested to contribute to various cancer-related processes, including therapeutic resistance. However, the precise mechanisms remain elusive. Using a well-defined drug-gene pair, we identified an enhancer region for dihydropyrimidine dehydrogenase (DPD, DPYD gene) expression that is relevant to the metabolism of the anti-cancer drug 5-fluorouracil (5-FU). Using reporter systems, CRISPR genome-edited cell models, and human liver specimens, we demonstrated in vitro and vivo that genotype status for the common germline variant (rs4294451; 27% global minor allele frequency) located within this novel enhancer controls DPYD transcription and alters resistance to 5-FU. The variant genotype increases recruitment of the transcription factor CEBPB to the enhancer and alters the level of direct interactions between the enhancer and DPYD promoter. Our data provide insight into the regulatory mechanisms controlling sensitivity and resistance to 5-FU. [ABSTRACT FROM AUTHOR]

A number of activated carbon fibers (ACF) were prepared by activation with steam, Phosphoric acid, or Zinc Chloride. Their reduction-adsorption behavior for Pt(IV) was studied using scanning electron microscopy, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy. The results show that Pt ions in solution can be adsorbed by ACFs and reduced to metallic platinum. The reduction–adsorption capacity of ACF for Pt could be greater than 200 mg/g. Generally, higher specific surface area or lower electrode potential produces a higher capacity. Most of the adsorbed platinum ions were reduced into metallic platinum, and about 25% of platinum atoms remained as Pt(II) or Pt(IV). XRD examination showed that the Pt particles on the ACF surface were crystallized when heated to 673 K. [ABSTRACT FROM AUTHOR]

The Prolyl hydroxylase 1 (EGLN2) is known to affect tumorigenesis by regulating the degradation of hypoxiainducible factor. Polymorphisms in EGLN2 may facilitate cancer cell survival under hypoxic conditions and directly associate with cancer susceptibility. Here, we examined the contribution of a 4-bp insertion/deletion polymorphism (rs10680577) within the distal promoter of EGLN2 to the risk of hepatocelluar carcinoma (HCC) in Chinese populations. The contribution of rs10680577 to HCC risk was investigated in 623 HCC cases and 1,242 controls and replicated in an independent case--control study consisting of 444 HCC cases and 450 controls. Logistic regression analysis showed that the deletion allele of rs10680577 was significantly associated with increased risk for HCC occurrence in both case--control studies [OR = 1.40; 95% confidence interval (CI) = 1.18- 1.66, P < 0.0001; OR = 1.49; 95% CI = 1.18-1.88, P = 0.0007]. Such positive association was more pronounced in current smokers (OR=3.49, 95% CI=2.24-5.45) than nonsmokers (OR=1.24, 95% CI=1.03-1.50; heterogeneity P = 0.0002). Genotype--phenotype correlation studies showed that the deletion allele was significantly correlated with higher expression of both EGLN2 and RERT-IncRNA [a long noncoding RNA whose sequence overlaps with Ras-related GTP-binding protein 4b (RAB4B) and EGLN2)] in vivo and in vitro. Furthermore, RERT-IncRNA expression was also significantly correlated with EGLN2 expression in vivo, consistent with in vitro gain-of-function study that showed overexpressing RERT-IncRNA upregulated EGLN2. Finally, in silico prediction suggested that the insertion allele could disrupt the structure of RERT-IncRNA. Taken together, our findings provided strong evidence for the hypothesis that rs10680577 contributes to hepatocarcinogenesis, possibly by affecting RERT-IncRNA structure and subsequently EGLN2 expression, making it a promising biomarker for early diagnosis of HCC. [ABSTRACT FROM AUTHOR]