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Feng L.,Minhang District Central Hospital | Xie Y.,Minhang District Central Hospital | Zhang H.,Minhang District Central Hospital | Wu Y.,Shanghai JiaoTong University
Medical Oncology | Year: 2012

MicroRNAs (miRNAs) have emerged as posttranscriptional regulators that are critically involved in the pathogenesis of a number of human cancers. Recently, cyclin-dependent kinase 6 (CDK6) is found to be up-regulated in several types of human tumors and has been implicated in cancer initiation and progression. We have identified miR-107 as a potential regulator of CDK6 expression. A bioinformatics search revealed a putative target site for miR-107 within the CDK6 3′ untranslated region. Expression of miR-107 in gastric cancer cell lines was found inversely correlated with CDK6 expression. miR-107 could significantly suppress CDK6 3′ UTR luciferase reporter activity, and this effect was not detectable when the putative 3′ UTR target site was mutated. Consistent with the results of the reporter assay, ectopic expression of miR-107 reduced both mRNA and protein expression levels of CDK6, inhibited proliferation, induced G1 cell cycle arrest, and blocked invasion of the gastric cancer cells. Our results suggest that miR-107 may have a tumor suppressor function by directly targeting CDK6 to inhibit the proliferation and invasion activities of gastric cancer cells. © Springer Science+Business Media, LLC 2011. Source

Feng L.,Minhang District Central Hospital | Xie Y.,Minhang District Central Hospital | Zhang H.,Minhang District Central Hospital | Wu Y.,Shanghai JiaoTong University
Biochemical and Biophysical Research Communications | Year: 2011

The expression of N-myc downstream-regulated gene 2 (NDRG2) is present in normal tissues but low or undetectable in various cancers and thus poses a potential tumor suppressor gene. However, the expression of NDRG2 in colorectal tissues remains unknown. Here, our results showed that NDRG2 was down-regulated in colorectal cancer compared to benign colorectal tissues by using immunohistochemical staining and semi-quantitative RT-PCR analyses. Bisulfite sequencing analysis showed that the reduced NDRG2 expression was accompanied by de novo DNA methylation at the NDRG2 promoter. We also found that microRNA-650 (miR-650) targets a homologous DNA region in the promoter region of the NDRG2 gene and represses its expression at the transcriptional level. Reporter assay with 3'untranslated region of NDRG2 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-650, providing strong evidence that miR-650 is a direct regulator of NDRG2. In conclusion, these results suggest that NDRG2 expression is regulated by promoter methylation and miR-650 in human colorectal cancer cells, and endogenous small noncoding RNA induced control of transcription may be a potential system for expressional regulation in human colorectal cancer cells. © 2011 Elsevier Inc. Source

Wang Q.-B.,Minhang District Central Hospital | Zhu H.,Fudan University | Liu H.-L.,Minhang District Central Hospital | Zhang B.,Minhang District Central Hospital | Zhang B.,Shanghai JiaoTong University
Hepatology | Year: 2012

A meta-analysis was performed to assess and compare the accuracies of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) for the staging of hepatic fibrosis. Online journal databases and a manual search from January 2000 to May 2011 were used. We identified 41 studies, but only 14 met the criteria to perform a meta-analysis assessing MRE (five trials) or DWI (10 trials). Fibrosis was categorized by redistribution into five stages according to histopathological description. A bivariate binomial model was used to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from which diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (sROC) were derived to indicate the diagnostic accuracy of imaging modalities. With MRE, the sensitivity, specificity, DOR, PLR, NLR, and area under sROC curve (with 95% CIs) for staging F0 ~ F1 versus F2 ~ F4 and F0 ~ F2 versus F3 ~ F4 were 0.94 (0.81-0.98), 0.95 (0.87-0.98), 20 (7-57), 0.06 (0.02-0.22), 317 (55-1,796), 0.98 (0.97-0.99) and 0.92 (0.85-0.96), 0.96 (0.91-0.98), 21 (10-45), 0.08 (0.04-0.16), 251 (103-609), and 0.98 (0.96-0.99), respectively; and with DWI, these values were 0.77 (0.71-0.82), 0.78 (0.69-0.85), 3 (2-5), 0.30 (0.22-0.40), 12 (6-21), 0.83 (0.79-0.86) and 0.72 (0.60-0.81), 0.84 (0.77-0.89), 5 (3-7), 0.34 (0.23-0.50), 13 (6-29), and 0.86 (0.83-0.89), respectively. A z test demonstrated that MRE had a significantly higher accuracy than DWI in those indicators (P < 0.05). Conclusion: MRE is more reliable for staging hepatic fibrosis, compared with DWI, with a high combination of sensitivity, specificity, likelihood ratios, DOR, and area under sROC curve. © 2012 American Association for the Study of Liver Diseases. Source

Dong W.,Zhengzhou University | Feng L.,Minhang District Central Hospital | Xie Y.,Pathology | Zhang H.,Minhang District Central Hospital | Wu Y.,Shanghai JiaoTong University
Cancer Science | Year: 2011

LMX1A is epigenetically inactivated in cervical cancer. However, the expression and methylation status of LMX1A in gastric cancer tissues remains unknown. In the present study, we found that the expression of LMX1A was significantly decreased in gastric cancer tissues compared with normal tissues. A statistically significant inverse association was found between the LMX1A methylation status and expression of LMX1A in tumor tissues (P=0.008). Restoration of LMX1A induced cell apoptosis and suppressed anchorage-independent growth, suggesting LMX1A may be a potential biomarker for gastric cancer. © 2010 Japanese Cancer Association. Source

Chen Q.-H.,Minhang District Central Hospital | Wang Q.-B.,Minhang District Central Hospital | Zhang B.,Shanghai JiaoTong University
Tumor Biology | Year: 2014

Common functional polymorphisms in the promoter region of microRNAs (miRNAs), based on multiple lines of evidence, might participate in transcriptional regulation and other biological processes, which interact to increase the risk of developing breast cancer. Since 2005, many studies have investigated the association between breast cancer risk and common single nucleotide polymorphisms (SNPs) in miRNAs. However, the findings of several meta-analyses are inconclusive or ambiguous. The aim of this Human Genome Epidemiology meta-analysis was to determine more precisely the relationship between common miRNA polymorphisms and breast cancer risk. Twelve case-control studies with a total of 7,170 breast cancer patients and 8,783 healthy controls were included. Eight SNPs in miRNA genes were examined. When all eligible studies were pooled in the metaanalysis, the miR-196a-2 rs11614913*T, miR-499 rs3746444*T, and miR-605 rs2043556*A alleles predicted a decreased risk of breast cancer among Asians, while not Caucasians. In addition, the miR-27a rs895919*C allele might be a protective factor for breast cancer among Caucasians. However, for the miR-146a rs2910164 (G>C), miR-149 rs2292832 (G>T), miR-373 rs12983273 (C>T), and miR-423 rs6505162 (C>A) polymorphisms, we failed to find any significant association with the risk of breast cancer in any genetic model. In conclusion, the current meta-analysis supports that the miR-196a-2 rs11614913*T, miR-499 rs3746444*T, miR-605 rs2043556*A, and miR-27a rs895919*C alleles might be protective factors for breast cancer. Source

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