IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation

Chen, Feng,Zhu, Hai-Hong,Zhou, Lin-Fu,Wu, Shan-Shan,Wang, Jing,Chen, Zhi Korean Society for Biochemistry and Molecular Bion 2010 Experimental and molecular medicine Vol.42 No.7

The scaffold protein IQGAP1 shows elevated levels in several cancer types, but its expression in hepatocellular carcinoma is unknown. We found that 58% of human hepatocellular carcinoma tissue samples had increased IQGAP1 expression compared to adjacent normal tissue. Overexpressing IQGAP1 raised the in vivo tumorigenicity of hepatocellular carcinoma cells, and forced overexpression of IQGAP1 in vitro stimulated cell proliferation. Cell growth was reduced by knockdown or mutation of IQGAP1, or by treatment of cells with a phosphotidylinositol 3-kinase inhibitor. To determine the mechanism by which IQGAP1 overexpression affected hepatocellular carcinoma cells, we confirmed its interaction in these cells with mammalian target of rapamycin (mTOR), a serine/threonine kinase that integrates signals about nutrient and energy status with downstream effectors that influence cell division. In addition, we discovered a new interaction involving IQGAP1, mTOR and Akt, which is a downstream target of mTOR. Akt phosphorylation on Ser-473, which is catalyzed by mTOR and required for Akt activation, increased with increasing amounts of IQGAP1, and decreased with IQGAP1 mutation. We hypothesize that IQGAP1 is a scaffold that facilitates mTOR and Akt interaction.

IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation

Feng Chen,Zhi Chen,Hai-Hong Zhu,Lin-Fu Zhou,Shan-Shan Wu,Jing Wang 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.7

The scaffold protein IQGAP1 shows elevated levels in several cancer types, but its expression in hepatocellular carcinoma is unknown. We found that 58%of human hepatocellular carcinoma tissue samples had increased IQGAP1 expression compared to adjacent normal tissue. Overexpressing IQGAP1 raised the in vivo tumorigenicity of hepatocellular carcinoma cells, and forced overexpression of IQGAP1 in vitro stimulated cell proliferation. Cell growth was reduced by knockdown or mutation of IQGAP1, or by treatment of cells with a phosphotidylinositol 3-kinase inhibitor. To determine the mechanism by which IQGAP1 overexpression affected hepatocellular carcinoma cells,we confirmed its interaction in these cells with mammalian target of rapamycin (mTOR), a serine/threonine kinase that integrates signals about nutrient and energy status with downstream effectors that influence cell division. In addition, we discovered a new interaction involving IQGAP1, mTOR and Akt, which is a downstream target of mTOR. Akt phosphorylation on Ser-473, which is catalyzed by mTOR and required for Akt activation, increased with increasing amounts of IQGAP1, and decreased with IQGAP1 mutation. We hypothesize that IQGAP1 is a scaffold that facilitates mTOR and Akt interaction.

The Prognostic Value of Treatment-Related Lymphopenia in Nasopharyngeal Carcinoma Patients

Li-Ting Liu,Qiu-Yan Chen,Lin-Quan Tang,Shan-Shan Guo,Ling Guo,Hao-Yuan Mo,Ming-Yuan Chen,Chong Zhao,Xiang Guo,Chao-Nan Qian,Mu-Sheng Zeng,Jin-Xin Bei,Jing Tan,Shuai Chen,Ming-Huang Hong,Jian-Yong Shao 대한암학회 2018 Cancer Research and Treatment Vol.50 No.1

Purpose This study was conducted to evaluate the prognostic value of treatment-related lymphopenia in patients with nasopharyngeal carcinoma (NPC). Materials and Methods A total of 413 consecutive stage II-IVb NPC patients treated with concurrent chemoradiotherapy (CCRT) were enrolled. The overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test. Results A minimum (mini)–absolute lymphocyte counts (ALC) of < 390 cells/μL or ALC after 3 months of CCRT (post3m-ALC) < 705 cells/μL was significantly associated with worse outcome than mini-ALC ! 390 cells/μL (OS, p=0.002; PFS, p=0.005; DMFS, p=0.004) or post3m-ALC ! 705 cells/μL (OS, p < 0.001; PFS, p < 0.001; DMFS, p=0.001). Patients with lymphopenia (mini-ALC < 390 cells/μL and post3m-ALC < 705 cells/μL) had a worse prognosis than those without lymphopenia (mini-ALC ! 390 cells/μL and post3m-ALC ! 705 cells/μL) (OS, p < 0.001; PFS, p < 0.001; DMFS, p < 0.001). Multivariate analysis revealed that post3m-ALC was an independent prognostic factor for OS (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.12 to 2.78; p=0.015), PFS (HR, 1.86; 95% CI, 1.23 to 2.82; p=0.003), and DMFS (HR, 1.87; 95% CI, 1.13 to 3.08; p=0.014). Multivariate analysis also revealed that patients with lymphopenia had a high risk of death (HR, 3.79; 95% CI, 1.75 to 8.19; p=0.001), disease progression (HR, 2.93; 95% CI, 1.59 to 5.41; p=0.001), and distant metastasis (HR, 3.89; 95% CI, 1.67 to 9.10; p=0.002). Multivariate analysis performed with time dependent Cox regression demonstrated ALC was an independent prognostic factor for OS (HR, 0.995; 95% CI, 0.991 to 0.999; p=0.025) and PFS (HR, 0.993; 95% CI, 0.988 to 0.998; p=0.006). Conclusion Treatment-related lymphopenia was a poor prognostic factor in NPC patients.

Prolactin Inhibits BCL6 Expression in Breast Cancer Cells through a MicroRNA-339-5p-Dependent Pathway

Hong Yan,Min Zhao,Shan Huang,Ping Chen,Wen-yong Wu,Jin Huang,Zheng-sheng Wu,Qiang Wu 한국유방암학회 2016 Journal of breast cancer Vol.19 No.1

Purpose: Prolactin (PRL) plays a critical role in breast cancer progression by activating its cognate receptor and promotes the growth and differentiation of breast cancer cells. Studies have shown that B-cell lymphoma 6 (BCL6) is the target gene of microRNA- 339-5p (miR-339-5p) and that BCL6 expression contributes to breast cancer progression. Herein, we identified PRL as a potent suppressor of BCL6 expression in human breast cancer cells. Methods: Western blotting and quantitative reverse transcription-polymerase chain reaction were used to investigate molecular mechanisms underlying miR-339-5p expression and BCL6 manipulation in MCF-7, T47D, and SKBR3 breast cancer cells. Phenotypic changes in these breast cancer cell lines were assessed by performing cell viability (MTT), colony formation, migration, and invasion assays. Results: PRL suppressed BCL6 protein and mRNA expression and upregulated miR-339-5p expression in MCF-7 and T47D breast cancer cells. Selective downregulation of miR-339-5p expression significantly reversed PRL-induced suppression of BCL6 mRNA and protein expression. Exogenous PRL stimulation significantly decreased the proliferation, colony formation, migration, and invasion of breast cancer cells, and suppression of miR-339-5p expression reversed these processes in vitro. Conclusion: These results indicated that PRL inhibited BCL6 expression and regulated breast cancer progression through a miR-339-5p-dependent pathway.

Temporal distribution, influencing factors and pollution sources of urban ambient air quality in Nanchong, China

Hong Zhou,Youping Li,Huifang Liu,Zhongyu Fan,Jie Xia,Shanli Chen,Yuxiang Zheng,Xiaocui Chen 대한환경공학회 2015 Environmental Engineering Research Vol.20 No.3

The PM10, SO₂ and NO₂ mass concentrations were obtained over five years from monitoring stations across Nanchong, a southwest city in China. Changes in urban air quality over time, as well as the factors influencing that change, were evaluated based on air pollutant concentrations, the Air Pollution Index (API), and the Comprehensive Pollution Index (P). The results showed that the total annual mean PM10, SO₂ and NO₂ concentrations over the five years studied were 61.1±1.1, 45.0±3.9 and 34.9±4.9 μg·m-3, respectively. The annual mean concentrations displayed a generally decreasing trend; lower than the annual mean second-level air quality limit. Meanwhile, the annual mean API values were in a small range of 52-53, the air quality levels were gradeⅡ, and P values were 1.06-1.21 less than the slight level (P ≤ 1.31). Total monthly mean PM10, SO₂, NO₂ concentrations, and API and P values were consistently higher in winter and spring than during autumn and summer. The results of a correlation analysis showed that temperature and pressure were the major meteorological factors influencing pollution levels. Pollution sources included industrial coal and straw burning, automobiles exhaust and road dust, fireworks, and dust storms.

Flood Hydrograph Simulation Using a New Flood Stochastic Simulation Model

Chen Guo xin,An Shan fu,Wang Qiong,Jee Hong kee 대한토목학회 2006 대한토목학회 학술대회 Vol.2006 No.10

The infection status of anisakid larvae in marine fish and cephalopods from the Bohai Sea, China and their taxonomical consideration

Hong-Wei MA,Tai-Jing JIANG,Fu-Shi QUAN,Xiao-Guang CHEN,Hui-dong WANG,Yun-Shu ZHANG,Ming-Shan CUI,Wen-Yan ZHI,Dian-Chen JIANG 대한기생충학열대의학회 1997 The Korean Journal of Parasitology Vol.35 No.1

Genetic Diversity and Structure of Cordyceps sinensis Populations from Extensive Geographical Regions in China as Revealed by Inter-Simple Sequence Repeat Markers

Hong-Hui Liang,Zhou Cheng,Xiao-Ling Yang,Shan Li,Zu-Quan Ding,Tong-Shui Zhou,Wen-Ju Zhang,Jia-Kuan Chen 한국미생물학회 2008 The journal of microbiology Vol.46 No.5

Cordyceps sinensis is one of the most valuable medicinal caterpillar fungi native to China. However, its productivity is extremely limited and the species is becoming endangered. The genetic diversity of eighteen C. sinensis populations across its major distributing regions in China was evaluated by inter-simple sequence repeat (ISSR) markers. A total of 141 markers were produced in 180 individuals from the 18 populations, of which 99.3% were polymorphic. The low average of Shannon (0.104) and Nei index (0.07) of the 18 populations indicates that there are little genetic variations within populations. For all 18 populations, estimates of total gene diversity (HT), gene diversity within populations (HS), coefficient of genetic differentiation (GST), and gene flow (Nm) were 0.170, 0.071, 0.583, and 0.357, respectively. This pattern suggests that the genetic diversity of C. sinensis is low and most of the ISSR variations are found among populations with little gene exchange. The 18 populations are divided into five groups based on the genetic distance and the grouping pattern matches with the geographic distribution along the latitudinal gradient. The five groups show obvious difference in the GST and Nm values. Therefore, the genetic diversification of C. sinensis populations may be determined by geographic isolation and the combined effects of life history characters and the interaction with host insect species. The information illustrated by this study is useful for selecting in situ conservation sites of C. sinensis.

Association of XRCC3 Thr241Met Polymorphisms and Gliomas Risk: Evidence from a Meta-analysis

Liang, Hong-Jie,Yan, Yu-Lan,Liu, Zhi-Ming,Chen, Xu,Peng, Qi-Liu,Wang, Jian,Mo, Cui-Ju,Sui, Jing-Zhe,Wu, Jun-Rong,Zhai, Li-Min,Yang, Shi,Li, Tai-Jie,Li, Ruo-Lin,Li, Shan,Qin, Xue Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Met polymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphism and gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of nine case-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found that XRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10, 95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC: OR=1.29, 95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was found in Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36-2.36, P=0.00; TT vs. TC/CC: OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20). This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especially for Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scale and well-designed studies are needed to confirm our results.

Grub polypeptide extracts protect against oxidative stress through the NRF2-ARE signaling pathway

Jingyang Chen,Yingjian Sun,Shan Huang,Hong Shen,Yongjie Chen 한국통합생물학회 2021 Animal cells and systems Vol.25 No.6

Grub polypeptide extracts (GPEs) have antioxidant effects; however, their underlying molecular mechanisms are unknown. This study explored the antioxidant molecular mechanism of GPE via the nuclear factor-erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) signaling pathway in C2C12 muscle satellite cells exposed to oxidative stress. The effects of GPE/or H2O2 on C2C12 were investigated by the MTT (3- (4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) viability assay and immunofluorescence and small interfering RNA (siRNA) analyses. The cell viability, cell damage, intracellular reactive oxygen species (ROS) levels, and NRF2 signaling pathways related to proteins were measured. GPE significantly increased the antioxidant capacity of cells, evident by increased cell viability and decreased lactate dehydrogenase leakage, DNA damage, malondialdehyde content, and ROS level. GPE also markedly increased mRNA expression levels and activities of antioxidant enzymes including superoxidase 1 and 2, catalase, and glutathione peroxidase. In addition, GPE increased the gene and protein expression of NRF2 and heme oxygenase 1 by promoting NRF2 translocation from the cytoplasm to the nucleus and activating NRF2-ARE signaling pathways. The antioxidant effects of GPE through these signaling pathways were further confirmed by NRF2-specific siRNA silencing. Thus, GPE enhances antioxidant capacity and alleviates oxidative damage of C2C12 cells via the NRF2-ARE signaling pathway.