Esophageal cancer is the sixth leading cause of death from cancer and one of the least studied cancers worldwide. The global microRNA expression profile of esophageal cancer has not been reported previously. Here, for the first time, we have investigated expressed microRNAs in cryopreserved esophageal cancer tissues using advanced microRNA microarray techniques. Our microarray analyses identified seven microRNAs that could distinguish malignant esophageal cancer lesions from adjacent normal tissues. Some microRNAs could be correlated with the different clinicopathologic classifications. High expression of hsa-miR-103/107 correlated with poor survival by univariate analysis as well as by multivariate analysis. These results indicate that microRNA expression profiles are important diagnostic and prognostic markers of esophageal cancer, which might be analyzed simply using economical approaches such as reverse transcription-PCR.
MicroRNAs (miRNAs) play important roles in the posttranscriptional regulation of gene expression. Recent evidence has indicated the pathological relevance of miRNA dysregulation in hepatitis virus infection; however, the roles of microRNAs in the regulation of hepatitis B virus (HBV) expression are still largely unknown. In this study we identified that miR-373 was up-regulated in HBV-infected liver tissues and that the members of the miRs-371-372-373 (miRs-371-3) gene cluster were also significantly co-up-regulated in HBV-producing HepG2.2.15 cells. A positive in vivo association was identified between hepatic HBV DNA levels and the copy number variation of the miRs-371-3 gene cluster. The enhanced expression of miRs-372/373 stimulated the production of HBV proteins and HBV core-associated DNA in HepG2 cells transfected with 1.33HBV. Further, nuclear factor I/B (NFIB) was identified to be a direct functional target of miRs-372/373 by in silico algorithms and this was subsequently confirmed by western blotting and luciferase reporter assays. Knockdown of NFIB by small interfering RNA (siRNA) promoted HBV expression, whereas rescue of NFIB attenuated the stimulation in the 1.33HBV-transfected HepG2 cells. Conclusion: Our study revealed that miRNA (miRs-372/373) can promote HBV expression through a pathway involving the transcription factor (NFIB). This novel model provides new insights into the molecular basis in HBV and host interaction. (HEPATOLOGY 2011;54:808-819) H epatitis B virus (HBV) is a 3.2 kb circular hepadnavirus that transcribes four major RNA molecules that encode a viral X protein, surface proteins, core proteins, and a reverse transcriptase. The longest 3.5 kb RNA also acts as a pregenomic RNA (pgRNA) intermediate for the reverse replication. Four promoters and two enhancers have been found to regulate the viral gene transcription.1 After HBV infection, most adults produce a self-limited infection with a quick viral clearance; however, others become carriers or develop Abbreviations: CNV, copy number variation; ENI-Cp, enhancer I and core promoter of hepatitis B virus; FFPE, formalin-fixed, paraffin embedded; HBeAg, hepatitis B virus e antigen; HBsAg, hepatitis B virus surface antigen; HBV, hepatitis B virus; miRNA, microRNA; miRs-371-3, miRs-371-372-373; NFIB, nuclear factor I/B; qPCR, quantitative real-time polymerase chain reaction; SAM, significance analysis of microarrays; UTR, untranslated region.From the
ObjectiveTo reveal the familial prevalence and molecular variation of α- and β-globin gene mutations in Guangdong Province.MethodsA total of 40,808 blood samples from 14,332 families were obtained and analyzed for both hematological and molecular parameters.ResultsA high prevalence of α- and β-globin gene mutations was found. Overall, 17.70% of pregnant women, 15.94% of their husbands, 16.03% of neonates, and 16.83% of couples (pregnant women and their husbands) were heterozygous carriers of α- or β-thalassemia. The regions with the highest prevalence were the mountainous and western regions, followed by the Pearl River Delta; the region with the lowest prevalence was Chaoshan. The total familial carrier rate (both spouses were α- or β-thalassemia carriers) was 1.87%, and the individual carrier rates of α- and β-thalassemia were 1.68% and 0.20%, respectively. The total rate of moderate-to-severe fetal thalassemia was 12.78% among couples in which both parents were carriers.ConclusionsThere was a high prevalence of α- and β-thalassemia in Guangdong Province. This study will contribute to the development of thalassemia prevention and control strategies in Guangdong Province.
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