ATM Signaling Pathway Is Implicated in the SMYD3-mediated Proliferation and Migration of Gastric Cancer Cells

Wang, Lei,Wang, Qiu-Tong,Liu, Yu-Peng,Dong, Qing-Qing,Hu, Hai-Jie,Miao, Zhi,Li, Shuang,Liu, Yong,Zhou, Hao,Zhang, Tong-Cun,Ma, Wen-Jian,Luo, Xue-Gang The Korean Gastric Cancer Association 2017 Journal of gastric cancer Vol.17 No.4

Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined. Materials and Methods: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Additionally, an MTT assay and clonogenic assay were performed to evaluate cell proliferation, and a cell cycle analysis was performed by propidium iodide staining. Furthermore, the expression of genes implicated in the ataxia telangiectasia mutated (ATM) pathway and proteins involved in cell cycle regulation were detected by polymerase chain reaction and western blot analyses. Results: Compared with control cells, gastric cancer cells transfected with si-SMYD3 showed lower migration and invasion abilities (P<0.05), and the absence of SMYD3 halted cells in G2/M phase and activated the ATM pathway. Furthermore, the opposite patterns were observed when SMYD3 was elevated in normal gastric cells. Conclusions: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas.

SMYD3-associated pathway is involved in the anti-tumor effects of sulforaphane on gastric carcinoma cells

Qing-Qing Dong,Qiu-Tong Wang,Lei Wang,Ya-Xin Jiang,Mei-Ling Liu,Hai-Jie Hu,Yong Liu,Hao Zhou,Hong-Peng He,Tong-Cun Zhang,Xuegang Luo 한국식품과학회 2018 Food Science and Biotechnology Vol.27 No.4

Sulforaphane (SFN), a natural compound derived from cruciferous vegetables, has been proved to possess potent anti-cancer activity. SMYD3 is a histone methyltransferase which is closely related to the proliferation and migration of cancer cells. This study showed that SFN could dose-dependently induce cell cycle arrest, stimulate apoptosis, and inhibit proliferation and migration of gastric carcinoma cells. Accompanied with these anticancer effects, SMYD3 and its downstream genes, myosin regulatory light chain 9, and cysteine-rich angiogenic inducer 61, was downregulated by SFN. Furthermore, overexpression of SMYD3 via transfection could abolish the effects of SFN, suggesting that SMYD3 might be an important mediator of SFN. To the best of our knowledge, this is the first report describing the role of SMYD3 in the anti-cancer of SFN. These findings might throw light on the development of novel anti-cancer drugs and functional food using SFN-rich cruciferous vegetables.

Maximum likelihood estimation method for dual-rate Hammerstein systems

Dong-Qing Wang,Zhen Zhang,Jin-Yun Yuan 제어·로봇·시스템학회 2017 International Journal of Control, Automation, and Vol.15 No.2

For a dual-rate sampled Hammerstein controlled autoregressive moving average (CARMA) system, thispaper uses the polynomial transformation technology to obtain its dual-rate bilinear identification model whichis suitable for the available dual-rate sampled-data, uses the maximum likelihood principle to construct a unifiedparameter vector of all parameters and an information vector formed by the derivative of the noise variable tothe unified parameter vector, and directly identifies the parameters of the linear block and the nonlinear blockfor the dual-rate Hammerstein CARMA system. The unified parameter vector contains the minimum number ofthe unknown parameters, and the proposed maximum likelihood estimation algorithm has higher computationalefficiency than the over-parameterization model based least squares algorithm.

Biomechanical Role of Nucleotomy in Vibration Characteristics of Human Spine

Qing-Dong Wang,Li-Xin Guo 한국정밀공학회 2021 International Journal of Precision Engineering and Vol.22 No.7

Nucleotomy is a common surgical procedure for the treatment of lumbar diseases. It may accelerate degeneration in the operated disc and decreased segmental stability, and this has been widely concerned by scholars for many years. However, under whole-body vibration, nucleotomy how to affect the vibration characteristics of the lumbar spine and complications is urgent to know. A three-dimensional nonlinear osteoligamentous finite element model of the intact L1-sacrum lumbar spine with muscles was established, and the nucleus of the L4–L5 disc was removed in the nucleotomy model. The lower surface of the sacrum was fully constrained for all models. A 5 Hz, 40 N sinusoidal vertical load supplemented with a 400 N preload was applied at L1 to simulate the vertical vibration of the human body. The results showed that nucleotomy increased the dynamic responses of the discs such as stress in the annulus ground substance and intradiscal pressure both in the maximum value and vibration amplitude. The maximum endplate stresses and corresponding vibration amplitudes of the denucleated L4–L5 level increased because of nucleotomy. Nucleotomy decreased the maximum response values of disc height and segmental lordosis but increased the corresponding amplitudes. Therefore, these findings imply that nucleotomy may increase the risk of developing complications such as disc degeneration, adjacent segment disease, endplate degeneration, lumbar instability, nerve root compress, isthmic spondylolisthesis, and lumbar disc herniation under whole-body vibration. This study reveals insights into the effect of the nucleotomy on the vibration characteristics of the lumbar spine and provides new information toward the relationship between nucleotomy and complications.

Data Filtering based Least Squares Algorithms for Multivariable CARAR-like Systems

Dong-Qing Wang,Feng Ding,Da-Qi Zhu 제어·로봇·시스템학회 2013 International Journal of Control, Automation, and Vol.11 No.4

This paper focuses on the identification problem of multivariable controlled autoregressive autoregressive (CARAR-like) systems. The corresponding identification model contains a parameter vector and a parameter matrix, and thus the conventional least squares methods cannot be applied to directly estimate the parameters of the systems. By using the hierarchical identification principle, this paper presents a hierarchical generalized least squares algorithm and a filtering based hierarchical least squares algorithm for the multivariable CARAR-like systems. The simulation results show that the two hierarchical least squares algorithms are effective.

The method of geometric error measurement of NC machine tool based on the principle of space vector's direction measurement

Jin-Dong Wang,Qing-Jie Wang,Hai-Tao Li 한국정밀공학회 2019 International Journal of Precision Engineering and Vol.20 No.4

To achieve the quick and accurate calibration of the geometric errors of NC machine tool, a new method with laser tracker on the basis of space vector’s direction measurement principle is proposed in the paper. A series of measuring points are mounted on the moving part of the machine tool, and then adjacent measuring points are connected to form a space vector respectively. Due to the motion error of the machine tool, the direction of the vectors composed will be changed. Meanwhile, the deviation of vector’s direction only relates to angular displacement error rather than linear displacement error. Based on the characteristic, the change of vectors’ direction is measured by laser tracker based on the multi-station and time-sharing measurement during the motion of machine tool, and then the angular displacement errors and linear displacement errors of each axis can be accurately identified successively, which reduces the complexity of error identification. By establishing the mathematical model of geometric error measurement of machine tool based on the principle of space vector’s direction measurement, the base station calibration algorithm by measuring the motion of the designed precise turntable, the measuring point determination algorithm and geometric error separation algorithm are derived respectively, and the accuracy of these algorithms are verified by simulations. In addition, the results of the experiments show the feasibility of the proposed method.

ATM Signaling Pathway Is Implicated in the SMYD3-mediated Proliferation and Migration of Gastric Cancer Cells

Lei Wang,Qiu-Tong Wang,Yu-Peng Liu,Qing-Qing Dong,Hai-Jie Hu,Zhi Miao,Shuang Li,Yong Liu,Hao Zhou,Tong-Cun Zhang,Wen-Jian Ma,Xuegang Luo 대한위암학회 2017 Journal of gastric cancer Vol.17 No.4

Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined. Materials and Methods: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Additionally, an MTT assay and clonogenic assay were performed to evaluate cell proliferation, and a cell cycle analysis was performed by propidium iodide staining. Furthermore, the expression of genes implicated in the ataxia telangiectasia mutated (ATM) pathway and proteins involved in cell cycle regulation were detected by polymerase chain reaction and western blot analyses. Results: Compared with control cells, gastric cancer cells transfected with si-SMYD3 showed lower migration and invasion abilities (P<0.05), and the absence of SMYD3 halted cells in G2/M phase and activated the ATM pathway. Furthermore, the opposite patterns were observed when SMYD3 was elevated in normal gastric cells. Conclusions: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas.

A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host macrophages infected with Mycobacterium tuberculosis

Fei-yu Wang,Yu-qing Zhang,Xin-min Wang,Chan Wang,Xiao-fang Wang,Jiang-dong Wu,Fang Wu,Wan-jiang Zhang,Le Zhang 한국미생물학회 2016 The journal of microbiology Vol.54 No.4

Myeloid cell leukemia-1 (Mcl-1) plays an important role in various cell survival pathways. Some studies indicated that the expression of Mcl-1 was upregulated in host cells during infection with the virulent Mycobacterium tuberculosis strain, H37Rv. The present study was designed to investigate the effect of inhibiting Mcl-1 expression both in vivo and in vitro on apoptosis of host macrophages infected with M. tuberculosis using a small hairpin (sh)RNA. Mcl-1 expression was detected by the real time-polymerase chain reaction, western blotting, and immunohistochemistry. Flow cytometry and transmission electron microscopy were used to measure host macrophage apoptosis. We found elevated Mcl-1 levels in host macrophages infected with M. tuberculosis H37Rv. The expression of Mcl-1 was downregulated efficiently in H37Rv-infected host macrophages using shRNA. Knockdown of Mcl-1 enhanced the extent of apoptosis in H37Rv-infected host macrophages significantly. The increased apoptosis correlated with a decrease in M. tuberculosis colony forming units recovered from H37Rv-infected cells that were treated with Mcl-1-shRNA. Reducing Mcl-1 accumulation by shRNA also reduced accumulation of the anti-apoptotic gene, Bcl-2, and increased expression of the pro-apoptotic gene, Bax, in H37Rv-infected host macrophages. Our results showed that specific knockdown of Mcl-1 expression increased apoptosis of host macrophages significantly and decreased the intracellular survival of a virulent strain of M. tuberculosis. These data indicate that interference with Mcl-1 expression may provide a new avenue for tuberculosis therapy.

No Association Between the USP7 Gene Polymorphisms and Colorectal Cancer in the Chinese Han Population

Li, Xin,Wang, Yang,Li, Xing-Wang,Liu, Bao-Cheng,Zhao, Qing-Zhu,Li, Wei-Dong,Chen, Shi-Qing,Huang, Xiao-Ye,Yang, Feng-Ping,Wang, Quan,Wang, Jin-Fen,Xiao, Yan-Zeng,Xu, Yi-Feng,Feng, Guo-Yin,Peng, Zhi-Ha Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. USP7 is a very important protein with an important role in regulating the p53 pathway, which is critical for genomic stability and tumor suppression. We here genotyped eight SNPs within the USP7 gene and conducted a case-control study in 312 CRC patients and 270 healthy subjects in the Chinese Han population. No significant associations were found for any single SNP and CRC risk. Our data eliminate USP7 as a potential candidate gene towards for CRC in the Han Chinese population.

Antiproliferative activities of Garcinia bracteata extract and its active ingredient, isobractatin, against human tumor cell lines

Shen, Tao,Li, Wei,Wang, Yan-Yan,Zhong, Qing-Qing,Wang, Shu-Qi,Wang, Xiao-Ning,Ren, Dong-Mei,Lou, Hong-Xiang 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.3

In our cell based screening of antitumor ingredients from plants, the EtOH extract of Garcinia bracteata displayed antiproliferative effect against human lung adenocarcinoma A549 cells, human breast cancer MCF-7 cells, and human prostate cancer PC3 cells. Phytochemical investigation of this active extract produced nine ingredients, and their structures were established by analysis of MS and NMR spectra. Antiproliferative evaluation of isolated ingredients on A549, MCF-7 and PC3 cells indicated that a xanthone named isobractatin (1) exhibited potent antiproliferative activity against the above three human cancer cell lines with $IC_{50}$ values ranging from 2.90 to $4.15{\mu}M$. Treatment of PC3 cells with 1 led to an enhancement of the cell apoptosis, and arrested cell cycle in the G0/G1 phase. The G0/G1 phase cycle-related proteins analysis showed that the expressions of cyclins D1 and E were reduced by 1, whereas the protein level of cyclin dependent kinase (CDK) inhibitor P21 was induced. Additionally, 1 enhanced PC3 cell apoptosis by activations of Bax, caspases 3 and 9, and by inhibition of Bcl-2. Our combined data illustrated that isobractatin (1) was the antiproliferative ingredient of G. bracteata against three human cancer cell lines, which exerted its antiproliferatrive effect via cell cycle arrest and induction of apoptosis.