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Yang X.,Chengdu Medical College | Luo E.,The Fifth Peoples Hospital of Chengdu | Liu X.,Chengdu Medical College | Han B.,Chengdu Medical College | And 2 more authors.
BMC Cancer | Year: 2016

Background: The long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) plays a crucial role in cancer progression, which is regulated by the interferon regulatory factor-1 (IRF1) and up-streaming Akt activation. The present study evaluated the chemopreventive effects of delphinidin-3-glucoside (Dp), a major anthocyanin present in pigmented fruits and vegetables, on breast carcinogenesis, and investigate the role of the Akt/HOTAIR signaling pathway. Methods: Human breast epithelial cells MCF10A were treated with carcinogens (NNK and B[a]P) or co-treated with carcinogens plus Dp for 30 days. Then, the cancer-associated properties of the treated cells were evaluated to assess the carcinogenesis and the effects of Dp. HOTAIR levels were detected by qRT-PCR. The proteins expression was measured by western blots, immunofluorescence and immunohistochemistry. Xenografted tumors were made by implanting breast cancer cells MDA-MB-231-Luc-GFP in athymic mice. ChIP-qPCR analysis was used to detect the IRF1 binding to the HOTAIR promoter. Results: Carcinogens treatment induces apparent carcinogenic transformation in MCF10A cells including reduced dependence on growth factors, anchorage-independent cell growth and aberrant wound-healing ability, which is effectively suppressed by Dp co-treatment. The level of HOTAIR significantly increases in a time-dependent manner during chronic breast carcinogenesis. Dp treatment down-regulates HOTAIR expression in breast carcinogenesis and breast cancer cells. Furthermore, Dp administration inhibits the growth of xenografted breast tumors in athymic mice, and decreases HOTAIR in vivo. Further studies showed that Dp represses Akt activation, promotes IRF1 expression and increases IRF1 binding to the HOTAIR promoter. Silence of IRF1 expression via transfecting cells with IRF1 siRNAs significantly reduced the effects of Dp on HOTAIR, resulting in decreased cytotoxic effects of Dp on breast cancer cells. Conclusions: These data suggest the effective chemopreventive effect of Dp on breast carcinogenesis, in which down-regulation of HOTAIR plays a critical role. © 2016 The Author(s).


PubMed | The Fifth Peoples Hospital of Chengdu, Sichuan Cancer Hospital and Luzhou Medical College
Type: Journal Article | Journal: Cancer gene therapy | Year: 2016

Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck and is associated with a high rate of lymph node metastasis. The initial step in the metastasis and transition of tumors is epithelial-mesenchymal transition (EMT)-induced angiogenesis, which can be mediated by angiopoietin 2 (ANG2), a key regulatory factor in angiogenesis. In the present study, immunohistochemistry and real-time quantitative reverse transcriptase (qRT-PCR) were used to measure the expression of ANG2 in OSCC tissues. Plasmids encoding ANG2 mRNA were used for increased ANG2 expression in the OSCC cell line TCA8113. The short interfering RNA (siRNA)-targeting ANG2 mRNA sequences were used to inhibit ANG2 expression in TCA8113 cells. Subsequently, transwell assays were performed to examine the effects of ANG2 on TCA8113 cell migration and invasion. Furthermore, in vivo assays were performed to assess the effect of ANG2 on tumor growth. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays and immunohistochemistry were used to examine cell apoptosis and angiogenesis in tumor tissues, respectively. Finally, western blot analysis was performed to evaluate tumor formation-related proteins in OSCC tissues. We found that protein expression of ANG2 was remarkably upregulated in OSCC tissues. Overexpression of ANG2 increased the migration and invasion of TCA8113 cells by regulating EMT. Further investigations showed that overexpression of ANG2 increased tumor growth in nude mice, and angiogenesis of OSCC tissues increased in the presence of ANG2 overexpression. Overexpression of ANG2 also reduced cell apoptosis in tumor tissue cells. Finally, we found that overexpression of ANG2 resulted in changes in the expression of tumor formation-related proteins including vimentin, E-cadherin, Bim, PUMA, Bcl-2, Bax, Cyclin D1, PCNA and CD31. Our findings show that ANG2 has an important role in the migration and invasion of OSCC. More importantly, further investigations suggested that overexpression of ANG2 might increase OSCC metastasis by promoting angiogenesis in nude mice. This stimulatory effect could be achieved by inducing abnormal EMT and by reducing apoptosis and increasing proliferation of cells.


PubMed | Hubei University, The Fifth peoples Hospital of Chengdu, Chongqing Medical University, The Fifth peoples Hospital of Chongqing and University of Sichuan
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

Hepatocellular carcinoma (HCC) and hepatic cholangiocarcinoma (CC) are the most aggressive malignancies with a poor prognosis in humans, and hepatic cholangiocarcinoma (CC) exhibits greater malignant behaviour. Yes-associated protein (YAP) is an important downstream target of the Hippo signalling pathway. As an oncogene, it plays a vital role in the occurrence and development of tumours. Our study focuses on the clinical significance of YAP protein expression in HCC and CC. Furthermore, we sought to explore the different survival rates between HCC and CC. A total of 137 patients with HCC and 122 with CC after resection were evaluated by immunohistochemistry for the expression of YAP. Our results showed that positive expression rates of YAP were more frequently noted in CC 67.2% (82/122) than in HCC 56.9% (78/137) (P=0.024). High YAP expression in HCC and CC was significantly associated with tumour size (P<0.001 and P=0.019, respectively), liver cirrhosis (P=0.002 and P=0.009, respectively), vascular invasion (P=0.047 and P=0.018, respectively), multiplicity (P=0.019 and P=0.015, respectively), and intrahepatic metastasis (P = 0.015 and P=0.047, respectively). Importantly, recurrence-free survival and disease-specific survival rates were lower in CC with high YAP expression than in HCC with high YAP expression (P<0.001 and P<0.001, respectively). Overall, high YAP expression was more frequently found in CC than in HCC, and YAP overexpression was associated with poor survival rates in patients with HCC and CC. Targeting YAP treatment requires further prospective investigations in larger patient populations.


Sun Y.,the PLA General Hospital | Li D.G.,Chinese Academy of Sciences | Li Q.,The Fifth Peoples Hospital of Chengdu | Huang L.,The Fifth Peoples Hospital of Chengdu | And 3 more authors.
Journal of biological regulators and homeostatic agents | Year: 2015

Metabolic syndrome (MS), a series of physiological and metabolic disorders caused by insulin resistance, combines clinical syndrome of abdominal obesity, diabetes or impaired glucose regulation, dyslipidemia, hypertension and other metabolic diseases. Several studies have found that multiple single nucleotide polymorphism (SNP) exists in adiponectin gene (ADIPOQ) and some unusual mutations might be related to hypoadiponectinemia and MS. This study aims to explore the relationship between ADIPOQ gene polymorphism and lipid levels and diabetes. A total of 1,049 confirmed MS cases were selected for research. From the perspective of potential functional SNPs of ADIPOQ gene, tag SNPs, combined with environmental factors, we studied the relationship between ADIPOQ gene polymorphism and phenotype (serum adiponectin level) and further analyzed the correlation of ADIPOQ gene polymorphism and metabolic syndrome components so as to clear the relationship between ADIPOQ gene polymorphism and lipid levels and diabetes and at the same time provide a scientific basis for preventing primarily MS etiology and screening high-risk groups.


PubMed | Chinese Academy of Sciences, Beijing Center for Physical and Chemical Analysis, The Fifth Peoples Hospital of Chengdu and the PLA General Hospital
Type: Letter | Journal: Journal of biological regulators and homeostatic agents | Year: 2015

Metabolic syndrome (MS), a series of physiological and metabolic disorders caused by insulin resistance, combines clinical syndrome of abdominal obesity, diabetes or impaired glucose regulation, dyslipidemia, hypertension and other metabolic diseases. Several studies have found that multiple single nucleotide polymorphism (SNP) exists in adiponectin gene (ADIPOQ) and some unusual mutations might be related to hypoadiponectinemia and MS. This study aims to explore the relationship between ADIPOQ gene polymorphism and lipid levels and diabetes. A total of 1,049 confirmed MS cases were selected for research. From the perspective of potential functional SNPs of ADIPOQ gene, tag SNPs, combined with environmental factors, we studied the relationship between ADIPOQ gene polymorphism and phenotype (serum adiponectin level) and further analyzed the correlation of ADIPOQ gene polymorphism and metabolic syndrome components so as to clear the relationship between ADIPOQ gene polymorphism and lipid levels and diabetes and at the same time provide a scientific basis for preventing primarily MS etiology and screening high-risk groups.


Zhang F.,University of Sichuan | Tang X.,University of Sichuan | Cao H.,The Fifth Peoples Hospital of Chengdu | Qingguo L.,University of Sichuan | And 8 more authors.
International Journal of Medical Sciences | Year: 2012

Objective: We assessed the serum glucagon-like peptide-1 (GLP-1) levels for Chinese adults with pre-diabetes (PD) and newly-diagnosed diabetes mellitus (NDDM) during oral glucose tolerance test (OGTT). The relationships between total GLP-1 level and islet β cell function, insulin resistance (IR) and insulin sensitivity (IS) were also investigated. Methods: A 75g glucose OGTT was given to 531 subjects. Based on the results, they were divided into groups of normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined IGT (IFG+IGT) and NDDM. Total GLP-1 levels were measured at 0-and 2-hour during OGTT. Homeostasis model as-sessment of β cell function (HOMA-β), HOMA of insulin resistance (HOMA-IR), Gutt and Matsuda indexes were calculated. The relationships between GLP-1 level and β cell function, IR and IS were analyzed. Results: The levels of total fasting GLP-1 (FGLP-1), 2h GLP-1 (2hGLP-1) and 2hGLP-1 in-crements (ΔGLP-1) following OGTT reduced significantly in IFG+IGT and NDDM groups (P<0.005). HOMA-β, HOMA-IR, Gutt and Matsuda indexes demonstrated various patterns among NGT, isolated IFG, isolated IGT, IFG+IGT and NDDM groups (P<0.05). Spearman rank correlation analysis and multivariable linear regression model suggested that some levels of correlation between GLP-1 levels, ΔGLP-1 and β cell function, IR (P<0.05). Conclusions: The total GLP-1 levels and its response to glucose load decreased significantly in IFG+IGT group, compared to isolated IFG or IGT group. They were even similar to that of NDDM group. Moreover, there were observable correlations between impaired GLP-1 se-cretion and β cell function, IR and IS. © Ivyspring International Publisher.


Wang Z.,University of Sichuan | Wang Z.,The Fifth Peoples Hospital of Chengdu | Shu D.,University of Sichuan | Dong B.,University of Sichuan | And 2 more authors.
Archives of Gerontology and Geriatrics | Year: 2013

Objective: The goal of this study was to determine the prevalence and correlates of anxiety disorders among empty-nest older adults in Sichuan Province, China. Methods: The study population consisted of 352 subjects over the age of 60 who completed the Self-Rating Anxiety Scale (SAS), the Geriatric Depression Scale-Short Form (GDS-SF), the University of California, Los Angeles, Loneliness Scale (UCLA-LS), and the Mini-Mental State Examination (MMSE) questionnaires. The socio-demographic information, information on the subjects' general health, and their level of concern about health problems were obtained from self-reports. Results: In the study population, 30.11% of the empty-nest older adults showed anxiety-related symptoms or anxiety disorders, with a standardized score of 44.53 ± 11.01. The levels of anxiety were significantly different in terms of the patients' gender, educational level, occupation, residence, marital status, and income, but not in terms of their age. Patient anxiety had a significantly positive association with depression and loneliness but had a significantly negative association with the MMSE scores. Multiple regression analysis revealed that patients with depression, loneliness, and cognitive impairment, as well as patients who were female, living in rural areas, or living alone were at risk for anxiety disorders. Conclusions: Anxiety prevails among the empty-nest older adults in Sichuan Province and is mainly associated with health-related characteristics. Physicians should give special attention to older adults with depression, loneliness, and cognitive impairments, especially to women who live alone in rural areas. © 2012 Elsevier Ireland Ltd.


PubMed | University of Sichuan and The Fifth Peoples Hospital of Chengdu
Type: Journal Article | Journal: Oncology letters | Year: 2014

Human PPPDE peptidase domain-containing protein 1 (PPPDE1) is a recently identified protein; however, its exact functions remain unclear. In our previous study, the PPPDE1 protein was found to be decreased in certain cancer tissues. In the present study, a total of 96 pancreatic ductal carcinoma tissue samples and 31 normal tissues samples were assessed to investigate the distribution of plakoglobin and -catenin under the conditions of various PPPDE1 expression levels by means of immunohistochemistry. Generally, the staining of PPPDE1 was strong in normal tissues, but weak in cancer tissues. Plakoglobin was mainly distributed along the membrane and cytoplasm border in normal cells, but was less evident in the membranes of cancer cells. In particular, a greater percentage of cells exhibited low membrane plakoglobin expression in cancer tissue with low PPPDE1 expression (PPPDE1-low cancer) compared with that in cancer tissue with high PPPDE1 expression (PPPDE1-high cancer). The distribution of -catenin in normal tissues was similar to that of plakoglobin. However, -catenin was peculiarly prone to invade nucleus in PPPDE1-low cancer compared with PPPDE1-high cancer. Our data suggested potential links between PPPDE1 expression and the distribution of plakoglobin and -catenin in pancreatic ductal adenocarcinoma, providing insights into the role of PPPDE1 in the progression of pancreatic cancer.


PubMed | University of Sichuan and The Fifth Peoples Hospital of Chengdu
Type: Journal Article | Journal: Oncology letters | Year: 2017

Human desumoylating isopeptidase 2 (DESI-2) is a member of the DESI family and contains a conserved PPPDE1 domain. Previous studies have demonstrated that DESI-2 overexpression may induce cell apoptosis. In the present study, differentially expressed genes were analyzed using a transcription microarray in DESI-2 overexpressing PANC-1 pancreatic cancer cells. A total of 45,033 genes were examined by microarray, which identified 1,766 upregulated and 1,643 downregulated genes. A series of altered signaling pathways were analyzed, in which certain essential signaling factors, including retinoid X receptor (RXR), BH3 interacting-domain death agonist, Ras homolog gene family member A (RhoA) and Rho-associated protein kinase, were further investigated at the protein level. The release of cytochrome


Gan M.,Sichuan Academy of Medical science and Sichuan Provincial Peoples Hospital | Yin X.,The Fifth Peoples Hospital of Chengdu
Cell Biochemistry and Biophysics | Year: 2014

This research designed to explore the antitumor activity of puerarin against human mantle cell lymphoma (MCL). Cell proliferation and apoptosis were assessed by MTS and flow cytometry. Caspase-3, -8, and -9 activities were assessed with the colorimetric caspase protease assay. Apoptotic proteins like PARP, cyclin D1, Bcl-2 family, XIAP, and cIAP I were researched by western blot. The PI3K inhibitor LY294002 was used to investigate the possible mechanism relating the PI3K/Akt signaling pathway. Puerarin in vitro inhibited proliferation and induced apoptosis of Z138 cells. Expressions of PI3K and p-Akt were downregulated by puerarin. Puerarin negatively regulated NF-κB activity by inhibiting NF-κB phosphorylation with nuclear translocation inhibition. This kind of effects was correlated with the suppression of expression of cyclin D1, BAX, Bcl-2, XIAP etc. This function was modulated by the PI3K inhibitor. Our results demonstrated that puerarin can induce growth arrest and apoptosis in MCL cells and that the mechanism may involve the NF-κB signaling pathway. Puerarin may have therapeutic applications in the treatment of MCL. © 2014 Springer Science+Business Media New York.

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