1.
MiRNAs as biomarkers of myocardial infarction: a meta-analysis.
Cheng, C, Wang, Q, You, W, Chen, M, Xia, J
PloS one. 2014;(2):e88566
Abstract
BACKGROUND Recent studies have demonstrated that acute myocardial infarction induces a distinctive miRNA signature, suggesting that miRNAs may serve as diagnostic markers. Although many studies have investigated the use of miRNAs in the detection of cardiac injury, some had small sample sizes (<100 patients) or reported different results for the same miRNA. Here, the role of circulating miRNAs for use as biomarkers of myocardial infarction is summarized and analyzed. METHODS AND RESULTS Medline, SCI, Embase, and Cochrane databases were searched up to January 2013 for studies that evaluated associations between miRNAs and myocardial infarction. Relevant publications were identified by searching for combinations of "myocardial infarction," "miRNAs," and their synonyms. Methodological quality was scored using a standardized list of criteria, and diagnostic performance was assessed using estimates of test sensitivity and specificity. These values were summarized using summary receiver-operating characteristic curves. Nineteen studies met the inclusion criteria: 15 studies reported sensitivity, specificity, and AUC, but 4 studies did not. Total miRNAs: sensitivity: 0.78 (95%CI: 0.77-0.80; P = 0.0000); specificity: 0.82 (95%CI: 0.80-0.83; P = 0.0000). miR-499: sensitivity: 0.88 (95%CI:0.86-0.90; P = 0.0000); specificity: 0.87 (95%CI:0.84-0.90; P = 0.0000). miR-1: sensitivity: 0.63 (95%CI:0.59-0.66; P = 0.0000); specificity: 0.76 (95%CI:0.71-0.80; P = 0.0000). miR-133a: sensitivity: 0.89 (95%CI:0.83-0.94; P = 0.0047); specificity: 0.87 (95%CI:0.79-0.92; P = 0.0262). miR-208b: sensitivity: 0.78 (95%CI:0.76-0.81; P = 0.0581); specificity: 0.88 (95%CI:0.84-0.91; P = 0.0000). The correlation between miRNAs and other diagnostic biomarkers of myocardial infarction was obvious. CONCLUSION MiRNAs, especially miR-499 and miR-133a, may be suitable for use as diagnostic biomarkers of myocardial infarction.
2.
Histone demethylase retinoblastoma binding protein 2 is overexpressed in hepatocellular carcinoma and negatively regulated by hsa-miR-212.
Liang, X, Zeng, J, Wang, L, Fang, M, Wang, Q, Zhao, M, Xu, X, Liu, Z, Li, W, Liu, S, et al
PloS one. 2013;(7):e69784
Abstract
BACKGROUND The H3K4 demethylase retinoblastoma binding protein 2 (RBP2) is involved in the pathogenesis of gastric cancer, but its role and regulation in hepatocellular carcinoma (HCC) is unknown. We determined the function of RBP2 and its regulation in HCC in vitro and in human tissues. METHODS We analyzed gene expression in 20 specimens each of human HCC and normal liver tissue by quantitative real-time PCR and immunohistochemistry. Proliferation was analyzed by foci formation and senescence by β-galactosidase staining. Promoter activity was detected by luciferase reporter assay. RESULTS The expression of RBP2 was stronger in cancerous than non-cancerous tissues, but that of its binding microRNA, Homo sapiens miR-212 (hsa-miR-212), showed an opposite pattern. SiRNA knockdown of RBP2 significantly upregulated cyclin-dependent kinase inhibitors (CDKIs), with suppression of HCC cell proliferation and induction of senescence. Overexpression of hsa-miR-212 suppressed RBP2 expression, with inhibited cell proliferation and induced cellular senescence, which coincided with upregulated CDKIs; with low hsa-miR-212 expression, CDKIs were downregulated in HCC tissue. Inhibition of hsa-miR-212 expression upregulated RBP2 expression. Luciferase reporter assay detected the direct binding of hsa-miR-212 to the RBP2 3' UTR. CONCLUSIONS RBP2 is overexpressed in HCC and negatively regulated by hsa-miR-212. The hsa-miR-212-RBP2-CDKI pathway may be important in the pathogenesis of HCC.