MicroRNAs are involved in several aspects of cardiac hypertrophy, including cardiac growth, conduction, and fibrosis. However, their effects on the regulation of the cardiomyocyte cytoskeleton in this pathological process are not known. Here, with microRNA microarray and small RNA library sequencing, we show that microRNA-1 (miR-1) is the most abundant microRNA in the human heart. By applying bioinformatic target prediction, a cytoskeleton regulatory protein twinfilin-1 was identified as a potential target of miR-1. Overexpression of miR-1 not only reduced the luciferase activity of the reporter containing the 3′ untranslated region of twinfilin-1 mRNA, but also suppressed the endogenous protein expression of twinfilin-1, indicating that twinfilin-1 is a direct target of miR-1. miR-1 was substantially downregulated in the rat hypertrophic left ventricle and phenylephrine-induced hypertrophic cardiomyocytes, and accordingly, the protein level of twinfilin-1 was increased. Furthermore, overexpression of miR-1 in hypertrophic cardiomyocytes reduced the cell size and attenuated the expression of hypertrophic markers, whereas silencing of miR-1 in cardiomyocytes resulted in the hypertrophic phenotype. In accordance, twinfilin-1 overexpression promoted cardiomyocyte hypertrophy. Taken together, our results demonstrate that the cytoskeleton regulatory protein twinfilin-1 is a novel target of miR-1, and that reduction of miR-1 by hypertrophic stimuli induces the upregulation of twinfilin-1, which in turn evokes hypertrophy through the regulation of cardiac cytoskeleton.

Background and ObjectivesRapid on-site evaluation (ROSE) during endoscopic ultrasonography-guided fine needle aspiration (EUS–FNA) of pancreatic masses has been reported to be associated with improved adequacy and diagnostic yield. However, recent observational data on the impact of ROSE have reported conflicting results. A meta-analysis and systematic review was therefore conducted to evaluate the contribution of ROSE during EUS-FNA of pancreatic masses.MethodA systematic search was conducted in MEDLINE/Pubmed and EMBASE databases for studies comparing the efficacy of ROSE between patients in two cohorts. Outcomes considered included diagnostic adequate rate, diagnostic yield, number of needle passes, pooled sensitivity and specificity. Findings from a random-effects model were expressed as pooled risk difference (RD) with 95% confidence intervals (CIs).ResultsA total of 7 studies (1299 patients) was finally included and further analyzed in the current meta-analysis. EUS-FNA with ROSE could not improve diagnostic adequacy (RD = 0.05, 95% CI: -0.01–0.11) and diagnostic yield (RD = 0.04 95%CI: -0.05, 0.13). The number of needle passes showed no statistically significant difference with and without ROSE (RD = -0.68 95%CI: -2.35, 0.98). The pooled sensitivity and specificity of ROSE group were 0.91 (95%CI: 0.87, 0.94) and 1 (95%CI: 0.94, 1.00). The pooled sensitivity and specificity of non-ROSE group were 0.85 (95%CI: 0.80, 0.89) and 1 (95%CI: 0.95, 1.00). ROSE group and non-ROSE group showed comparable sensitivity and specificity.ConclusionCompared to historical reports of its clinical efficacy in patients with pancreatic lesions, ROSE may be not associated with an improvement of diagnostic yield, adequate rate, pooled sensitivity and specificity.

The current evidence does not indicate a statistically significant superiority of ELAPE over conventional APE in terms of CRM positivity and intra-operative bowel perforation.

Cancers with aberrant expression of Serine/threonine kinase 33 (STK33) has been reported to be particularly aggressive. However, its expression, clinical significance, and biological functions in gastric cancer remain largely unknown. In the present study, we determined the expression and function of STK33 in gastric cancer and delineated the clinical significance of the Krüppel-like factor 4 (KLF4)/STK33 signaling pathway. STK33 expression and its association with multiple clinicopathologic characteristics were analyzed immunohistochemically in human gastric cancer specimens. STK33 knockdown and overexpression were used to dissect the underlying mechanism of its functions in gastric cancer cells. Regulation and underlying mechanisms of STK33 expression by KLF4 in gastric cancer cells were studied using cell and molecular biological methods. Drastically higher expression of STK33 was observed in gastric cancer and gastric intraepithelial neoplasia tissues compared with adjacent normal gastric tissues. Increased STK33 expression correlated directly with tumor size, lymph node, and distant metastasis; and patients with low STK33 expression gastric cancer were predicted to have a favorable prognosis. Enforced expression of STK33 promoted gastric cancer cell proliferation, migration, and invasion and, whereas reduced STK33 did the opposite. Moreover, STK33 promoted epithelial-mesenchymal transition (EMT) Mechanistically, KLF4 transcriptionally inhibited STK33 expression in gastric cancer cells. KLF4-mediated inhibition of gastric cancer cell invasion was reversed by upregulation of STK33 expression. STK33 has pro-tumor function and is a critical downstream mediator of KLF4 in gastric cancer. STK33 may serve as a potential prognostic marker and therapeutic target for gastric cancer. .