Yi-Xin Zeng

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (271)1284.59 Total impact

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    ABSTRACT: Tumor-derived exosomes contain biologically active proteins and messenger and microRNAs (miRNAs). These particles serve as vehicles of intercellular communication and are emerging mediators of tumorigenesis and immune escape. Here, we isolated 30-100 nm exosomes from the serum of patients with nasopharyngeal carcinoma (NPC) or the supernatant of TW03 cells. Increased circulating exosome concentrations were correlated with advanced lymphoid node stage and poor prognosis in NPC patients (P< 0.05). TW03-derived exosomes impaired T-cell function by inhibiting T-cell proliferation and Th1 and Th17 differentiation and promoting Treg induction by NPC cells in vitro. These results are associated with decreases in ERK, STAT1, and STAT3 phosphorylation and increases in STAT5 phosphorylation in exosome-stimulated T-cells. TW03-derived exosomes increased the proinflammatory cytokines IL-1β, IL-6, and IL-10 but decreased IFNγ, IL-2, and IL-17 release from CD4+ or CD8+ T-cells. Furthermore, five commonly over-expressed miRNAs were identified in the exosomes from patient sera or NPC cells: hsa-miR-24-3p, hsa-miR-891a, hsa-miR-106a-5p, hsa-miR-20a-5p, and hsa-miR-1908. These over-expressed miRNA clusters down-regulated the MARK1 signaling pathway to alter cell proliferation and differentiation. Overall, these observations reveal the clinical relevance and prognostic value of tumor-derived exosomes and identify a unique intercellular mechanism mediated by tumor-derived exosomes to modulate T-cell function in NPC.
    Oncotarget 06/2014; · 6.64 Impact Factor
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    ABSTRACT: Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 [times] 10-8 to 9.22 [times] 10-21) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the in
    Nature Genetics 06/2014; 46(6):533-542. · 35.21 Impact Factor
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    ABSTRACT: Although microRNA-30a (miR-30a) has been shown to regulate cancer metastasis, the molecular mechanism has not yet been clearly elucidated in nasopharyngeal carcinoma (NPC). The present study was to investigate the miR-30a expression pattern and its potential functions and further to identify its target gene and corresponding clinical applications in NPC. MiR-30a was identified to be down-regulated in NPC primary tumors compared with metastatic tumors using quantitative real-time PCR. Furthermore, over-expression of miR-30a transfected with precursor increased the ability of metastasis and invasion of NPC tumor cells in vivo and in vitro. E-cadherin was screened as a putative target gene of miR-30a by computational algorithms. Luciferase reporter assays showed that over-expression of miR-30a directly reduced the activity of a luciferase transcript combined with the 3'-untranslated region (3'-UTR) of E-cadherin. Kaplan-Meier survival analysis and log-rank test were analyzed for 1077 NPC patients for overall survival, indicating that a high expression of E-cadherin was beneficial for NPC prognosis (P = 0.001). Importantly, NPC patients with high expression of E-cadherin had much lower risk of poor prognosis (hazard ratio = 0.757, P = 0.017) using multivariate analysis. In conclusion, miR-30a could play an important role in regulating NPC metastasis and potentially provide useful guidelines for individualized therapy.
    Experimental Biology and Medicine 05/2014; · 2.80 Impact Factor
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial-mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK-STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target.
    Cell cycle (Georgetown, Tex.) 04/2014; 13(12). · 5.24 Impact Factor
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    ABSTRACT: Triple-negative breast cancer (TNBC) is a high risk form of this disease, even after surgery, due to the absence of targets for hormone treatment and anti-Her-2 therapy. Chemotherapy is the main therapeutic strategy for such breast cancer patients although the outcome is often unsatisfactory. Thus, the development of combination adjuvant therapies is essential for improved prognosis in TNBC patients. In this study, we investigated the efficacy of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for post-mastectomy TNBC patients. From 2008 to 2012, 90 post-mastectomy TNBC patients were included in this retrospective study: 45 cases received chemotherapy alone or with sequential radiotherapy; a further 45 cases received chemotherapy with/without radiotherapy and sequential CIK infusion. Survival analysis showed significantly higher disease-free survival (DFS) rate and overall survival (OS) rates in the CIK treatment group compared with the control group (p = 0.0382, p = 0.0046, respectively; log-rank test). Multivariate survival analysis showed that CIK adjuvant treatment was an independent prognostic factor for OS of TNBC patients. In subgroup analyses, CIK adjuvant treatment significantly increased the DFS rate of patients with pathological grade III, and significantly increased the OS rate of patients in N1, N2, N3-stage, IIB, III TNM stage and with pathological grade III. These data indicate that adjuvant CIK treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of TNBC patients, particularly those with lymph node metastasis, advanced TNM-stage and poor pathological grade.
    Clinical Cancer Research 03/2014; · 7.84 Impact Factor
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    Wei Zhang, Chao-Nan Qian, Yi-Xin Zeng
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    ABSTRACT: Once considered a taboo topic or stigma, cancer is the number one public health enemy in the world. Once a product of an almost untouchable industry, tobacco is indisputably recognized as a major cause of cancer and a target for anti-cancer efforts. With the emergence of new economic powers in the world, especially in highly populated countries such as China, air pollution has rapidly emerged as a smoking gun for cancer and has become a hot topic for public health debate because of the complex political, economic, scientific, and technological issues surrounding the air pollution problem. Does air pollution cause a wide spectrum of cancers? Should air pollution be considered a necessary evil accompanying economic transformation in developing countries? Is an explosion of cancer incidence coming to China and how soon will it arrive? What must be done to prevent this possible human catastrophe?
    Ai zheng = Aizheng = Chinese journal of cancer 03/2014;
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    ABSTRACT: Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size = -0.045 mm, P = 8.17×10-9). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45×10-9; 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
    PLoS Genetics 03/2014; 10(3):e1004089. · 8.52 Impact Factor
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    ABSTRACT: The goal of this study was to establish a plasma microRNA profile by use of next-generation sequencing that could aid in assessment of patient prognosis in nasopharyngeal carcinoma (NPC).METHODS: Two panels of NPC patients and healthy controls (HCs) were recruited for this study. We used deep sequencing to screen plasma microRNAs. Differentially expressed microRNAs were verified by quantitative real-time PCR (qPCR). Kaplan-Meier survival analysis with the log-rank test was used to compare overall survival (OS) and progression-free survival (PFS) between groups.RESULTS: Twenty-three plasma miRNAs with differential expression levels were selected for qPCR analysis on an independent set including 100 NPC patients and 55 HCs. NPC patients with low concentrations of miR-483-5p and miR-103 had better prognosis for 5-year OS than those with high concentrations (87.5% vs 55.8%, P < 0.001; 80.9% vs 62.3%, P = 0.031). Those with low concentrations of miR-29a and let-7c had poorer prognosis (54.8% vs 82.8%, P = 0.002; 56.3% vs 84.6%, P = 0.001). A 3-signature miRNA integrated with clinical stage was further identified in an independent set. We calculated a prognostic index score and classified patients into low-, medium-, and high-risk groups. Five-year OS among the 3 groups was significantly different (90.9%, 66.7%, and 23.8%; P < 0.001). By multivariate analysis, a high-risk score was the most significantly unfavorable prognostic factor independent of other clinical variables (P < 0.001, hazard ratio = 15.1, 95% CI = 5.2-43.9).CONCLUSIONS: Differentially expressed plasma miRNAs as identified by next-generation sequencing can be helpful for predicting survival in NPC patients.
    Clinical Chemistry 02/2014; · 7.15 Impact Factor
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    ABSTRACT: Twist is a key transcription activator of epithelial-mesenchymal transition (EMT). It remains unclear how Twist induces gene expression. Here we report a mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like breast cancer (BLBC). Twist contains a "histone H4-mimic" GK-X-GK motif that is diacetylated by Tip60. The diacetylated Twist binds the second bromodomain of BRD4, whose first bromodomain interacts with acetylated H4, thereby constructing an activated Twist/BRD4/P-TEFb/RNA-Pol II complex at the WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4 association reduced WNT5A expression and suppressed invasion, cancer stem cell (CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates that the interaction with BRD4 is critical for the oncogenic function of Twist in BLBC.
    Cancer cell 02/2014; 25(2):210-25. · 25.29 Impact Factor
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    ABSTRACT: The utility of circulating Epstein-Barr Virus (EBV) DNA as a tumor marker for nasopharyngeal carcinoma (NPC) detection suggests that it might improve the diagnostic performance of anti-EBV antibody markers in NPC screening. In this study, the authors evaluated whether circulating EBV DNA load is capable of distinguishing NPC patients from high-risk individuals who have positive anti-EBV antibodies. In a population-based NPC screening trial in Sihui City and Zhongshan City, Guangdong Province, China, the authors previously identified 862 high-risk participants with 2 screening markers, immunoglobulin A (IgA) antibodies to EBV capsid antigen (VCA/IgA) and nuclear antigen-1 (EBNA1/IgA). In the current study, real-time polymerase chain reaction was used to measure the baseline plasma EBV DNA load among 825 participants (97%). Follow-up was extended to the end of 2011 to evaluate the diagnostic and predictive values of plasma EBV DNA load. By using 0 copies/mL as the cutoff value, plasma EBV DNA had a sensitivity of 86.8% (33 of 38 patients) for NPC detected within the first year of follow-up, yielding a positive predictive value of 30% (33 of 110 participants) and a negative predictive value of 99.3% (696 of 701 participants). The patients who had early stage NPC had lower sensitivity (81.5%; 22 of 27 patients) than those who had advanced NPC (100%; 11 of 11 patients). For the 14 patients who had NPC detected after 1 year of follow-up, only 50% (7 of 14 patients) tested positive for EBV DNA at baseline. The plasma EBV DNA load may improve the accuracy of diagnosing NPC in high-risk individuals, but it appears to have limited value in screening patients who have early stage NPC and predicting NPC development. Cancer 2014. © 2014 American Cancer Society.
    Cancer 01/2014; · 5.20 Impact Factor
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    ABSTRACT: MicroRNA-214 (MiR-214) is aberrantly expressed in several human tumors such as ovarian cancer and breast cancer. However, the role of miR-214 in nasopharyngeal carcinoma (NPC) is still unknown. In this study, we report that miR-214 was overexpressed in NPC cell lines and tissues. Silencing of miR-214 by LNA-antimiR-214 in NPC cells resulted in promoting apoptosis and suppressing cell proliferation in vitro, and suppressed tumor growth in nude mice in vivo. Luciferase reporter assay was performed to identify Bim as a direct target of miR-214. Furthermore, this study showed that low Bim expression in NPC tissues correlated with poor survival of NPC patients. Taken together, our findings suggest that miR-214 plays an important role in NPC carcinogenesis.
    PLoS ONE 01/2014; 9(1):e86149. · 3.73 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) of colorectal cancer (CRC) have been conducted primarily in European descendants. In a GWAS conducted in East Asians, we first analyzed approximately 1.7 million single-nucleotide polymorphisms (SNPs) in four studies with 1,773 CRC cases and 2,642 controls. We then selected 66 promising SNPs for replication and genotyped them in three independent studies with 3,612 cases and 3,523 controls. Five SNPs were further evaluated using data from four additional studies including up to 3,290 cases and 4,339 controls. SNP rs7229639 in the SMAD7 gene was found to be associated with CRC risk with an odds ratio (95% confidence interval) associated with the minor allele (A) of 1.22 (1.15-1.29) in the combined analysis of all 11 studies (P = 2.93×10(-11) ). SNP rs7229639 is 2,487 bp upstream from rs4939827, a risk variant identified previously in a European-ancestry GWAS in relation to CRC risk. However, these two SNPs are not correlated in East Asians (r(2) = 0.008) nor in Europeans (r(2) = 0.146). The CRC association with rs7229639 remained statistically significant after adjusting for rs4939827 as well as three additional CRC risk variants (rs58920878, rs12953717, and rs4464148) reported previously in this region. SNPs rs7229639 and rs4939827 explained approximately 1% of the familial relative risk of CRC in East Asians. This study identifies a new CRC risk variant in the SMAD7 gene, further highlighting the significant role of this gene in the etiology of CRC. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 01/2014; · 6.20 Impact Factor
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is a common tumor in Southern China, but the oncogene mutational status of NPC patients has not been clarified. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined in 123 NPC patients. The relationships between mutational status and clinical data were assessed with a χ(2) or Fisher's exact test. Survival analysis was performed using the Kaplan-Meier method with the log-rank test. In 123 patients, 21 (17.1%) NPC tumors were positive for mutations in eight oncogenes: six patients had PIK3CA mutations (4.9%), five NRAS mutations (4.1%), four KIT mutations (3.3%), two PDGFRA mutations (1.6%), two ABL mutations (1.6%), and one with simultaneous mutations in HRAS, EGFR, and BRAF (1%). Patients with mutations were more likely to relapse or develop metastasis than those with wild-type alleles (P=0.019). No differences or correlations were found in other clinical characteristics or in patient survival. No mutations were detected in oncogenes AKT1, AKT2, CDK, ERBB2, FGFR1, FGFR3, FLT3, JAK2, KRAS, MET, and RET. These results demonstrate an association between NPC and mutations in NRAS, KIT, PIK3CA, PDGFRA, and ABL, which are associated with patient relapse and metastasis.
    OncoTargets and Therapy 01/2014; 7:457-67. · 2.07 Impact Factor
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    ABSTRACT: Epstein-Barr Virus (EBV) is a globally prevalent herpesvirus associated with infectious mononucleosis and many malignancies. The survey on EBV prevalence appears to be important to study EBV-related diseases and determine when to administer prophylactic vaccine. The purpose of this retrospective study was to collect baseline information about the prevalence of EBV infection in Chinese children.
    PLoS ONE 01/2014; 9(6):e99857. · 3.73 Impact Factor
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    ABSTRACT: Paclitaxel is a main ingredient in the combination chemotherapy treatment of advanced human cervical squamous cell carcinomas. We investigated the roles and underlying molecular mechanisms of PinX1 in cervical squamous cell carcinomas (CSCC) cells response to paclitaxel and its clinical significances. The expression dynamics of PinX1 was first examined by immunohistochemistry in 122 advanced CSCC patients treated with cisplatin/paclitaxel chemotherapy. The expression of PinX1 was significantly associated with the effects of cisplatin/paclitaxel chemotherapy in advanced CSCCs (P<0.05). High expression of PinX1 correlated with CSCC’s response to cisplatin/paclitaxel chemotherapy, and was an independent predictor of shortened survival (P<0.05). A series of in vivo and in vitro assays were performed to elucidate the function of PinX1 on CSCC cells chemosensitivity to paclitaxel and underlying mechanisms. In CSCC cells, the levels of PinX1 were only associated with the cytotoxicity and sensitivity of paclitaxel, in which knockdown of PinX1 dramatically enhanced paclitaxel cytotoxicity, whereas the reestablishment of PinX1 levels substantially reduced the paclitaxel-induced killing effect. In addition, we identified that the ability of PinX1 to stabilize the tension between sister kinetochores and maintain the spindle assembly checkpoint was the main reason CSCC cells undergo apoptosis when treated with paclitaxel, and further studies demonstrated that shortened distance between sisters kinetochores by nocodazole confers upon PinX1-replenished cells a sensitivity to the death inducing paclitaxel effects. Furthermore, our study of CSCC cells xenografts in nude mice confirmed the role of PinX1 in paclitaxel sensitivity in vivo. Our data reveal that PinX1 could be used as a novel predictor for CSCC patient response to paclitaxel, and the role of PinX1-mediated paclitaxel sensitivity might represent a new direction for the development of a new generation of microtubule drugs.
    Cancer Letters. 01/2014;
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    ABSTRACT: Lack of cellular differentiation is a key feature of nasopharyngeal carcinoma (NPC), but it also presents as a unique opportunity for intervention by differentiation therapy. Here using RNA-seq profiling analysis and functional assays, we demonstrate that reduced IKKα expression is responsible for the undifferentiated phenotype of NPC. Conversely, overexpression of IKKα induces differentiation and reduces tumorigenicity of NPC cells without activating NF-κB signalling. Importantly, we describe a mechanism whereby EZH2 directs IKKα transcriptional repression via H3K27 histone methylation on the IKKα promoter. The differentiation agent, retinoic acid, increases IKKα expression by suppressing EZH2-mediated H3K27 histone methylation, resulting in enhanced differentiation of NPC cells. In agreement, an inverse correlation between IKKα (low) and EZH2 (high) expression is associated with a lack of differentiation in NPC patient samples. Collectively, these findings demonstrate a role for IKKα in NPC differentiation and reveal an epigenetic mechanism for IKKα regulation, unveiling a new avenue for differentiation therapy.
    Nature Communications 01/2014; 5:3661. · 10.02 Impact Factor
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    ABSTRACT: Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerides into free fatty acids and glycerol. It has recently been found to be involved in cancer progression through the free fatty acid or endocannabinoid network after studies on its function in the endocannabinoid system. Here, we determined a role for MAGL in nasopharyngeal carcinoma (NPC), which is known for its high metastatic potential. Among the different NPC cells we tested, MAGL was highly expressed in high metastatic NPC cells, whereas low metastatic potential NPC cells exhibited lower expression of MAGL. Overexpression of MAGL in low metastatic NPC cells enhanced their motile behavior and metastatic capacity in vivo. Conversely, knockdown of MAGL reduced the motility of highly metastatic cells, reducing their metastatic capacity in vivo. Growth rate was not influenced by MAGL in either high or low metastatic cells. MAGL expression was associated with the epithelial-mesenchymal transition (EMT) proteins, such as E-cadherin, vimentin and Snail. It was also related to the sidepopulation (SP) of NPC cells. Our findings establish that MAGL promotes metastases in NPC through EMT, and it may serve as a target for the prevention of NPC metastases.
    International journal of clinical and experimental pathology. 01/2014; 7(7):3704-13.
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    ABSTRACT: The expression of hypoxia-induced factor (HIF)-1α is up-regulated in tumor microenvironments under hypoxia condition. However, the prognostic significance of HIF-1α in esophageal squamous cell carcinoma (ESCC) is still elusive. We measured the HIF-1α expression by immunochemistry in tumor specimens from 136 resected ESCC; in the current study, the HIF-1α expression in tumor cells was significantly associated with tumor stage (P = 0.003) and lymph node metastasis (P = 0.006); whereas the HIF-1α expression in tumor-infiltrating lymphocytes (TILs) had no relationship with patients' clinicopathological parameters. Patients with high HIF-1α expression in tumor cells or in TILs showed worse survival related to those with low HIF-1α expression. Multivariate analysis demonstrated that expression of HIF-1α in TILs was an independent factor for DFS (P = 0.007) and OS (P = 0.013). Additionally, the expression of HIF-1α in tumor cells was an independent factor for DFS (P = 0.037) and OS (P = 0.033) in locoregional ESCC patients, whereas the expression of HIF-1α in TILs was an independent factor for DFS (P = 0.048) and OS (P = 0.039) in metastatic ESCC patients. Correlation analysis revealed that expressions of HIF-1α in tumor cells and in TILs were positively correlated, and patients with combined high HIF-1α in both tumor cells and TILs had the worst survivals (P < 0.05). These findings suggest that the HIF-1α expressions in different cell populations of ESCC microenvironments have different clinical relevance and prognostic impact on patients.
    International journal of clinical and experimental pathology. 01/2014; 7(7):3887-97.
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    ABSTRACT: Determining the complex relationships between diseases, polymorphisms in human genes and environmental factors is challenging. Multifactor dimensionality reduction (MDR) has been proven to be capable of effectively detecting the statistical patterns of epistasis, although classification accuracy is required for this approach. The imbalanced dataset can cause seriously negative effects on classification accuracy. Moreover, MDR methods cannot quantitatively assess the disease risk of genotype combinations. Hence, we introduce a novel weighted risk score-based multifactor dimensionality reduction (WRSMDR) method that uses the Bayesian posterior probability of polymorphism combinations as a new quantitative measure of disease risk. First, we compared the WRSMDR to the MDR method in simulated datasets. Our results showed that the WRSMDR method had reasonable power to identify high-order gene-gene interactions, and it was more effective than MDR at detecting four-locus models. Moreover, WRSMDR reveals more information regarding the effect of genotype combination on the disease risk, and the result was easier to determine and apply than with MDR. Finally, we applied WRSMDR to a nasopharyngeal carcinoma (NPC) case-control study and identified a statistically significant high-order interaction among three polymorphisms: rs2860580, rs11865086 and rs2305806.
    International Journal of Molecular Sciences 01/2014; 15(6):10724-37. · 2.46 Impact Factor
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    ABSTRACT: PIN2/TRF1-interacting telomerase inhibitor1 (PinX1) was recently suggested as a putative tumor suppressor in several types of human cancer, based on its binding to and inhibition of telomerase. Moreover, loss of PinX1 has been detected in many human malignancies. However, the possible involvement of PinX1 and its clinical/prognostic significance in urothelial carcinoma of the bladder (UCB) are unclear. The PinX1 expression profile was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry (IHC) in UCB tissues and adjacent normal urothelial bladder epithelial tissues. PinX1 was overexpressed and silenced in UCB cell lines to determine its role in tumorigenesis, development of UCB, and the possible mechanism. PinX1 expression in UCB was significantly down-regulated at both mRNA and protein level as compared with that in normal urothelial bladder epithelial tissues. PinX1 levels were inversely correlated with tumor multiplicity, advanced N classification, high proliferation index (Ki-67), and poor survival (P < 0.05). Moreover, overexpression of PinX1 in UCB cells significantly inhibited cell proliferation in vitro and in vivo, whereas silencing PinX1 dramatically enhanced cell proliferation. Overexpression of PinX1 resulted in G1/S phase arrest and cell growth/proliferation inhibition, while silencing PinX1 led to acceleration of G1/S transition, and cell growth/proliferation promotion by inhibiting/enhancing telomerase activity and via the p16/cyclin D1 pathway. These findings suggest that down-regulation of PinX1 play an important role in the tumorigenesis and development of UCB and that the expression of PinX1 as detected by IHC is an independent molecular marker in patients with UCB.
    Molecular Cancer 11/2013; 12(1):148. · 5.13 Impact Factor

Publication Stats

4k Citations
1,284.59 Total Impact Points

Institutions

  • 2002–2014
    • Sun Yat-Sen University
      • • State Key Laboratory of Oncology
      • • Department of Medical Oncology
      Shengcheng, Guangdong, China
    • Zhongshan University
      中山, Guangdong, China
    • Sun Yat-Sen University of Medical Sciences
      • Cancer Center
      Guangzhou, Guangdong Sheng, China
  • 2000–2014
    • Sun Yat-Sen University Cancer Center
      • Department of Radiation Oncology
      Shengcheng, Guangdong, China
  • 2009–2013
    • State Key Laboratory of Medical Genetics of China
      Ch’ang-sha-shih, Hunan, China
    • Chongqing Medical University
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2012
    • University of Texas MD Anderson Cancer Center
      • Department of Molecular and Cellular Oncology
      Houston, Texas, United States
  • 2011
    • National Institute of Mental Health (NIMH)
      Maryland, United States
  • 2010
    • Henan Provincial People’s Hospital
      Cheng, Henan Sheng, China
  • 2008
    • Guangzhou University of Chinese Medicine
      Shengcheng, Guangdong, China
  • 2007
    • The University of Arizona
      • Department of Immunobiology
      Tucson, AZ, United States
  • 2004
    • Guangzhou University of Traditional Chinese Medicine
      Shengcheng, Guangdong, China