National Engineering Center for Biochip at Shanghai

Shanghai, China

National Engineering Center for Biochip at Shanghai

Shanghai, China
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Li T.,Peking University | Li T.,Tsinghua University | Wan B.,Chinese National Human Genome Center at Shanghai | Huang J.,National Engineering Center for Biochip at Shanghai | Zhang X.,Tsinghua University
Molecular Genetics and Genomics | Year: 2010

Proliferation of liver cells can be observed in hepatocarcinogenesis, at diVerent stages of liver development, and during liver regeneration after an injury. Does it imply that they share similar molecular mechanisms? Here, the transcriptional proWles of hepatocellular carcinoma (HCC), liver development, and liver regeneration were systematically compared as a preliminary attempt to answer this question. From the comparison, we found that advanced HCC mimics early development in terms of deprived normal liver functions and activated cellular proliferation, but advanced HCC and early development diVer in expressions of cancer-related genes and their transcriptional controls. HCC and liver regeneration demonstrate diVerent expression patterns as a whole, but regeneration is similar to dysplasia (pre-stage of HCC) in terms of their proximity to the normal state. In summary, of these three important processes, the carcinogenic progress carries the highest variance in expression; HCC pre-stage shares some resemblance with liver regeneration; and advanced HCC stage displays similarity with early development. © Springer-Verlag 2010.

Huang J.,Shanghai JiaoTong University | Huang J.,Chinese National Human Genome Center at Shanghai | Zheng D.-L.,Shanghai JiaoTong University | Zheng D.-L.,Chinese National Human Genome Center at Shanghai | And 11 more authors.
Journal of Clinical Investigation | Year: 2010

The epigenetic silencing of tumor suppressor genes is a crucial event during carcinogenesis and metastasis. Here, in a human genome-wide survey, we identified scavenger receptor class A, member 5 (SCARA5) as a candidate tumor suppressor gene located on chromosome 8p. We found that SCARA5 expression was frequently downregulated as a result of promoter hypermethylation and allelic imbalance and was associated with vascular invasion in human hepatocellular carcinoma (HCC). Furthermore, SCARA5 knockdown via RNAi markedly enhanced HCC cell growth in vitro, colony formation in soft agar, and invasiveness, tumorigenicity, and lung metastasis in vivo. By contrast, SCARA5 overexpression suppressed these malignant behaviors. Interestingly, SCARA5 was found to physically associate with focal adhesion kinase (FAK) and inhibit the tyrosine phosphorylation cascade of the FAK-Src-Cas signaling pathway. Conversely, silencing SCARA5 stimulated the signaling pathway via increased phosphorylation of certain tyrosine residues of FAK, Src, and p130Cas; it was also associated with activation of MMP9, a tumor metastasis-associated enzyme. Taken together, these data suggest that the plasma membrane protein SCARA5 can contribute to HCC tumorigenesis and metastasis via activation of the FAK signaling pathway.

Zhang F.-X.,CAS Shanghai Institutes for Biological Sciences | Liu X.-J.,CAS Shanghai Institutes for Biological Sciences | Gong L.-Q.,CAS Shanghai Institutes for Biological Sciences | Yao J.-R.,CAS Shanghai Institutes for Biological Sciences | And 8 more authors.
Journal of Neuroscience | Year: 2010

B-type natriuretic peptide (BNP) has been known to be secreted from cardiac myocytes and activate its receptor, natriuretic peptide receptor-A (NPR-A), to reduce ventricular fibrosis. However, the function of BNP/NPR-A pathway in the somatic sensory system has been unknown. In the present study, we report a novel function of BNP in pain modulation. Using microarray and immunoblot analyses, we found that BNP and NPR-A were expressed in the dorsal root ganglion (DRG) of rats and upregulated after intraplantar injection of complete Freund's adjuvant (CFA). Immunohistochemistry showed that BNP was expressed in calcitonin gene-related peptide (CGRP)-containing small neurons and IB4 (isolectin B4)-positive neurons, whereas NPR-A was present in CGRP-containing neurons. Application of BNP reduced the firing frequency of small DRG neurons in the presence of glutamate through opening large-conductance Ca2+- activated K+ channels (BKCa channels). Furthermore, intrathecal injection of BNP yielded inhibitory effects on formalin-induced flinching behavior and CFA-induced thermal hyperalgesia in rats. Blockade of BNP signaling by BNP antibodies or cGMP-dependent protein kinase (PKG) inhibitor KT5823 [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9, 12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i][1,6] benzodiazocine-10-carboxylic acid methyl ester] impaired the recovery from CFA-induced thermal hyperalgesia. Thus, BNP negatively regulates nociceptive transmission through presynaptic receptor NPR-A, and activation of the BNP/NPR-A/PKG/BKCa channel pathway in nociceptive afferent neurons could be a potential strategy for inflammatory pain therapy. Copyright © 2010 the authors.

Qu Y.,National Engineering Center for Biochip at Shanghai | He F.,National Engineering Center for Biochip at Shanghai | Chen Y.,National Engineering Center for Biochip at Shanghai
BMC Bioinformatics | Year: 2010

Background: Alternative splicing is an important mechanism that increases protein diversity and functionality in higher eukaryotes. Affymetrix exon arrays are a commercialized platform used to detect alternative splicing on a genome-wide scale. Two probe summarization algorithms, PLIER (Probe Logarithmic Intensity Error) and RMA (Robust Multichip Average), are commonly used to compute gene-level and exon-level expression values. However, a systematic comparison of these two algorithms on their effects on high-level analysis of the arrays has not yet been reported.Results: In this study, we showed that PLIER summarization led to over-estimation of gene-level expression changes, relative to exon-level expression changes, in two-group comparisons. Consequently, it led to detection of substantially more skipped exons on up-regulated genes, as well as substantially more included (i.e., non-skipped) exons on down-regulated genes. In contrast, this bias was not observed for RMA-summarized data. By using a published human tissue dataset, we compared the tissue-specific expression and splicing detected by Affymetrix exon arrays with those detected based on expressed sequence databases. We found the tendency of PLIER was not supported by the expressed sequence data.Conclusion: We showed that the tendency of PLIER in detection of alternative splicing is likely caused by a technical bias in the approach, rather than a biological bias. Moreover, we observed abnormal summarization results when using the PLIER algorithm, indicating that mathematical problems, such as numerical instability, may affect PLIER performance. © 2010 Qu et al; licensee BioMed Central Ltd.

Huang J.,Shanghai JiaoTong University | Huang J.,Chinese National Human Genome Center at Shanghai | Huang J.,National Engineering Center for Biochip at Shanghai | Huang J.,Guangdong Medical College | And 23 more authors.
Nature Genetics | Year: 2012

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC. © 2012 Nature America, Inc. All rights reserved.

Liu H.,National Engineering Center for Biochip at Shanghai | Liu H.,Chinese National Human Genome Center at Shanghai | Zhu L.,PLA Fourth Military Medical University | Liu B.,Shanghai JiaoTong University | And 6 more authors.
Cancer Letters | Year: 2012

Recent studies demonstrated that in several human malignancies aberrant expression profiles of circulating microRNAs (miRNAs) anticipate great cancer diagnostic potential. Here we showed that serum miR-378 could serve as a novel noninvasive biomarker in gastric cancer (GC) detection. Genome-wide miRNA expression profiles followed with Real-Time quantitative RT-PCR (qRT-PCR) assays revealed that miR-187 *, miR-371-5p and miR-378 were significantly elevated in GC patients. Further validation indicated that miR-378 alone could yields a ROC curve area of 0.861 with 87.5% sensitivity and 70.73% specificity in discriminating GC patients from healthy controls. Collectively, these data support our contention that serum miR-378 has strong potential as a novel noninvasive biomarker in gastric cancer detection. © 2011 Elsevier Ireland Ltd.

Li D.,Chongqing Cancer Institute | Zhou Q.,Chongqing Cancer Institute | Liu Y.,Chongqing Cancer Institute | Yang Y.,National Engineering Center for Biochip at Shanghai | Li Q.,Chongqing Cancer Institute
Medical Oncology | Year: 2012

This study aimed to investigate association between single-nucleotide polymorphisms (SNPs) of excision repair cross-complementing gene 1 (ERCC1), excision repair cross-complementing gene 2 (ERCC2), and X-ray repair cross-complementing group 1 (XRCC1) with sensitivity of advanced non-small cell lung cancer (NSCLC) patients to platinum-based chemotherapy. A total of 89 NSCLC patients were recruited and treated with two cycles of platinum-based chemotherapy. DNA was extracted from peripheral lymphocytes for detection of SNPs of ERCC1 Asn118Asn, ERCC2 Lys751Gln, and XRCC1 Arg399Gln. The overall response rate of these patients was 29.2%. There was no statistically significant difference of treatment response between the wild genotypes and the variant genotypes for the ERCC1 Asn118Asn and ERCC2 Lys751Gln gene. The distributions of genotypes XRCC1 Arg399Gln differed significantly between the response and non-response groups (76.9 vs. 23.1%, P = 0.001). The XRCC1 399Arg/Arg genotype carriers had a higher response rate than that of the Gln genotype carriers (OR = 4.81, 95%CI = 1.778-13.013, P = 0.002). The combination of the favorable genotypes of ERCC1, ERCC2, and XRCC1 had a higher response rate compared to that of patients with other genotypes. The combined polymorphisms of ERCC1, ERCC2, and XRCC1 may be associated with sensitivity of NSCLC to platinum-based chemotherapy. Further studies will verify these SNPs as biomarkers for prediction of platinum-based chemotherapy responses of NSCLC patients. © Springer Science+Business Media, LLC 2011.

Yu H.,Taizhou Peoples Hospital | Duan B.,Tongji University | Jiang L.,Taizhou Peoples Hospital | Lin M.,Taizhou Peoples Hospital | And 6 more authors.
American Journal of Translational Research | Year: 2014

MicroRNA-200c (miR-200c) influences sensitivity to chemotherapy and radiotherapy in vitro. This study was designed to investigate the prognostic potential of serum miR-200c in patients with advanced esophageal squamous cancer (ESCC). The serum levels of miR-200c was assayed by quantitative RT-PCR in 157 healthy subjects and 157 patients with advanced ESCC who were treated with platinum-based chemotherapy. The serum levels of miR-200c in advanced ESCC patients was significantly increased compared with those in controls (P < 0.001). Serum miR-200c expression was significantly associated with TNM stage (P = 0.037) and treatment response (P = 0.021). Patients with high expression of serum miR-200c had a higher risk for death than those with low expression of serum miR-200c (adjusted hazard ratios = 1.665, 95% confidence intervals: 1.135-2.443, P = 0.009). In conclusion, serum miR-200c may serve as predictor of survival for advanced ESCC and provide information for personalized therapy in advanced ESCC.

Fei T.,Tsinghua University | Xia K.,CAS Institute of Genetics and Developmental Biology | Li Z.,Tsinghua University | Zhou B.,CAS Institute of Genetics and Developmental Biology | And 7 more authors.
Genome Research | Year: 2010

Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation. Smad knockdown experiments further indicate that SMAD-mediated BMP signaling is largely required for differentiation-related processes rather than directly influencing self-renewal. Among the SMAD-associated genes, we further identified Dpysl2 (previously known as Crmp2) and the H3K27 demethylase Kdm6b (previously known as Jmjd3) as BMP4-modulated early neural differentiation regulators. Combined with computational analysis, our results suggest that SMAD-mediated BMP signaling balances self-renewal versus differentiation by modulating a set of developmental regulators. © 2010 by Cold Spring Harbor Laboratory Press.

Lin J.,Taizhou University | Huang Y.,Taizhou Hospital | Zhang X.,Taizhou Central Hospital | Chen J.,Taizhou Central Hospital | Sheng H.,National Engineering Center for Biochip at Shanghai
Pediatric Nephrology | Year: 2014

Background: Micro-RNAs (miRNAs) play important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate the association between three single nucleotide polymorphisms (SNPs) (mir-146a rs2910164, let-7a-2 rs1143770, miR-196a2 rs11614913) and susceptibility to and severity of childhood immunoglobulin A (IgA) nephropathy (IgAN).Methods: We genotyped three miRNA SNPs in two independent Han Chinese populations composed of 158 patients and 265 controls (discovery set), and 246 patients and 446 controls (validation set), respectively.Results: We found that rs2910164 was significantly associated with IgAN in the discovery but not the validation set. Combined analysis revealed that rs2910164 CC and CG genotypes were associated with increased risk of IgAN compared with the GG genotype [adjusted odds ratios (OR) = 1.684, 95 % confidence interval (CI)1.190–2.384, P = 0.003; adjusted OR = 1.472, 95 % CI 1.079–2.007, P = 0.015, respectively). We also found that the frequency of the rs2910164 CC genotype was significantly higher in patients with Haas grade III–V than in those with Haas grade I–II for all study populations (P < 0.05). The expression of miR-146a in normal renal tissues with CC genotype was lower than in those with a G allele (P = 0.038).Conclusions: These results indicated that rs2910164 may affect the susceptibility and severity of pediatric IgAN. Further studies are needed to validate these findings. © 2014, IPNA.

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