Expression of Snail1 in epithelial cells triggers an epithelial-mesenchymal transition (EMT). Here, we demonstrate that the synthesis of Zeb2, a transcriptional repressor of E-cadherin, is up-regulated after Snail1-induced EMT. Snail1 does not affect the synthesis of Zeb2 mRNA, but prevents the processing of a large intron located in its 5-untranslated region (UTR). This intron contains an internal ribosome entry site (IRES) necessary for the expression of Zeb2. Maintenance of 5-UTR Zeb2 intron is dependent on the expression of a natural antisense transcript (NAT) that overlaps the 5 splice site in the intron. Ectopic overexpression of this NAT in epithelial cells prevents splicing of the Zeb2 5-UTR, increases the levels of Zeb2 protein, and consequently down-regulates E-cadherin mRNA and protein. The relevance of these results is demonstrated by the strong association between NAT presence and conservation of the 5-UTR intron in cells that have undergone EMT or in human tumors with low E-cadherin expression. Therefore, the results presented in this article reveal the existence of a NAT capable of activating Zeb2 expression, explain the mechanism involved in this activation, and demonstrate that this NAT regulates E-cadherin expression.

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Background: Hypochondroplasia (HCH) is a skeletal dysplasia inherited in an autosomal dominant manner due, in most cases, to mutations in the fibroblast growth factor receptor 3 (FGFR3). Acanthosis nigricans (AN) is a velvety and papillomatous pigmented hyperkeratosis of the skin, which has been recognized in some genetic disorders more severe than HCH involving the FGFR3 gene. Objective and design: After initial study of the proband, who had been consulted for short stature and who also presented AN, the study was extended to the patient's mother and to 12 additional family members. Methods: Clinical, biochemical and radiological studies were performed on the family. In addition, exons 11 and 13 of FGFR3 were analyzed. Results: The proband and ten relatives presented HCH plus AN and the analysis of FGFR3 showed the p.Lys650Thr mutation. The members with normal phenotypes were non-carriers of the mutation. Conclusion: This is the first report of a large pedigree with the clinical phenotype of HCH plus AN due to a FGFR3 mutation, p.Lys650Thr. This finding demonstrates the coexistence of both conditions due to the same mutation and it might represent a true complex, which should be further established by searching for AN in mild HCH patients or for HCH in patients with AN.

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Aims: This study aimed to investigate the prognostic impact of the SYNTAX score II (SS-II) on ST-segment elevation myocardial infarction (STEMI) patients undergoing a primary percutaneous coronary intervention (pPCI). Methods and results: This retrospective cohort study included 1,689 patients with STEMI who underwent pPCI between January 2008 and December 2016. The patients were categorised into three groups based on SS-II tertiles (SS-II low tertile <24 [n=585], SS-II intermediate tertile ≥24 and ≤34 [n=567], and SS-II high tertile >34 [n=537]). In-hospital mortality was significantly lower in patients with low and mid SS-II when compared with high SS-II (0.7% vs 0.5% vs 16.4%, p=0.001). During follow-up (median 2.35 years), a high SS-II was positively correlated with MACE (12.3% for low SS-II vs 18.3% for mid SS-II vs 43.2% for high SS-II, p=0.001), all-cause mortality (1.5% vs 3.9% vs 14.2%, p=0.001) and heart failure (0.3% vs 2.7% vs 8.2%, p=0.001). The SS-II showed additive value on top of GRACE, anatomical SYNTAX score and residual SYNTAX score. Conclusions:The SS-II in patients with STEMI undergoing pPCI adds important prognostic information regarding midterm adverse outcomes, being an independent and powerful predictor of MACE, heart failure and all-cause mortality during follow-up.

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