scholarly journals Knockdown of Microtubule Associated Serine/threonine Kinase Like Expression Inhibits Gastric Cancer Cell Growth and Induces Apoptosis by Activation of ERK1/2 and Inactivation of NF-κB Signaling

2021 ◽  
Vol 41 (1) ◽  
pp. 108-117
Author(s):  
Cai-xia An ◽  
Shou-pin Xie ◽  
Hai-long Li ◽  
Yong-hua Hu ◽  
Rong Niu ◽  
...  

SummaryMicrotubule-associated serine/threonine kinase (MASTL) functions to regulate chromosome condensation and mitotic progression. Therefore, aberrant MASTL expression is commonly implicated in various human cancers. This study analyzed MASTL expression in gastric cancer vs. adjacent normal tissue for elucidating the association with clinicopathological data from patients. This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro. The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN, GEPIA, and Oncomine online databases. Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells. RT-qPCR, Western blotting, cell viability, cell counting, flow cytometric apoptosis and cell cycle, and colony formation assays were performed. MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue, and the MASTL expression was associated with advanced tumor stage, Helicobacter pylori infection and histological subtypes. On the other hand, knockdown of MASTL expression significantly reduced tumor cell viability and proliferation, and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis. At protein level, knockdown of MASTL expression enhanced levels of cleaved PARP1, cleaved caspase-3, Bax and p-ERK1/2 expression, but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells. MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression, whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis. Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.

Author(s):  
Mine Gulaboglu ◽  
Leyla Yildiz ◽  
Fehmi Celebi ◽  
Mustafa Gul ◽  
Kemal Peker

AbstractIt has been suggested that iodine plays an important role in gastric cancer. Gastric cancer ranks first among the cancers in the north-eastern Anatolia region, Turkey, where iodine deficiency is common. In this study, iodine levels were determined in gastric cancer and surrounding normal tissues in 19 patients with gastric cancer. Tissue iodine levels were determined by the Foss method based on the Sandell-Kolt-hoff reaction. Tissue iodine levels were lower in gastric cancer tissue (17.8±3.4ngI/mg protein, mean±SEM) compared with surrounding normal tissue (41.7±8.0ngI/mg protein) (p<0.001). There was positive correlation between the iodine levels in gastric cancer tissue and surrounding normal tissue (r=0.845, p<0.001). There was no significant difference in iodine levels in cancer and surrounding normal tissue between male and female subjects. The iodine deficiency in our region may be one of the factors for increased gastric cancer prevalence. Our results support the hypothesis that iodine plays an important role in gastric cancer development.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Changlu Gao ◽  
Qian Zhang ◽  
Deyang Kong ◽  
Di Wu ◽  
Changlei Su ◽  
...  

Mass spectrometry (MS) enables rapid and sensitive qualitative and quantitative analyses of biomolecules (proteins, peptides, oligosaccharides, lipids, DNA, and RNA), drugs, and metabolites. MS has become an essential tool in modern biomedical research, including the analysis of DNA methylation. DNA methylation has been reported in many cancers, suggesting that it can be utilized as an early biomarker to improve the early diagnosis rate. Using matrix-assisted laser desorption/ionization time-of-flight MS and MassCLEAVE reagent, we comparedNell-1hypermethylation levels among tumor tissues, paracarcinoma tissues, and normal tissues from gastric cancer patients. Almost 80% of the CpG sites in the amplicons produced were covered by the analysis. Our results indicate a significant difference in methylation status between gastric cancer tissue (a higher level) and normal tissue. The same trend was identified in gastric cancer tissue versus paracarcinoma tissue. We also detected lower relative expression ofNell-1by real-time PCR. Furthermore, immunohistochemical analyses revealed thatNell-1staining was less intense in cancer tissue relative to normal tissue and that the tumor cells had spread to the muscle layer. These findings may serve as a guide for the early diagnosis of gastric cancer.


2021 ◽  
Vol 76 (2) ◽  
pp. 122-126
Author(s):  
T. A. Bogush ◽  
E. M. Kapura-Brekhovskikh ◽  
A. A. Basharina ◽  
E. A. Bogush ◽  
V. Yu. Kirsanov ◽  
...  

2020 ◽  
Author(s):  
caixia An ◽  
hailong li ◽  
Rong Niu ◽  
xiaoguang liu ◽  
Yonghua Hu ◽  
...  

Abstract Background: Microtubule-associated serine/threonine kinase (MASTL) functions to regulate chromosome condensation and mitotic progression. Emerging reports showed that aberrant MASTL expression is commonly implicated in various human cancers and act as an oncogene. This study aimed to discover the potential significance of MASTL in gastric cancer, and to uncover relevant mechanisms. Methods: Lentivirus MASTL-shRNA was constructed and infected into MGC-803 cells to analysis its influences on cell proliferation by Green fluorescent protein (GFP)-based cellomics and colony formation assay, cell invasion and migration by transwell assay, apoptosis and cell cycle by flow cytometry detection, respectively. Nude mice and fluorescence imaging were used to characterize the regulation of tumor growth in vivo. Affymetrix mRNA microarray assay combined KEGG enrichment analysis were used to screen relevant molecules related to MASTL silencing. Finally,several aberrantly expressed genes were validated by quantitative reverse transcription PCR(RT-qPCR)and western blot detection. Results: Silencing MASTL significantly inhibited cell proliferation, migration and invasion, arrested cell cycle at G1 stage. Silencing MASTL reduced tumor growth in nude mice, and fluorescence imaging indicated that the total radiant efficiency of mice in the Lv-shMAST group was markedly reduced compared with in mice in the Lv-shCtrl group in vivo. Affymetrix mRNA microarray assay revealed that 124 genes upregulated, 167 genes downregulated. RT-qPCR and western blotting validation showed that cyclin dependent kinase 6(CDK6), bone morphogenetic protein 2(BMP2), snail family transcriptional repressor 2(SNAI2), phosphorylation-mechanistic target of rapamycin kinase (p-mTOR), phosphorylation-AKT serine/threonine kinase (p-AKT) and phosphorylation-p38 kinase (p-p38) are downregulated, and cyclin dependent kinase inhibitor 1A (CDKN1A) is upregulated. Conclusions: Silencing MASTL could significantly inhibit cell growth, migration ability, induce apoptosis, arrest cell cycle at G1 stage, and the mechanisms of which were mediated via inactivation of mTOR, AKT, p38 signal pathways.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yangyang Wang ◽  
Shuchang Wang ◽  
Qin Yang ◽  
Jun Li ◽  
Fengrong Yu ◽  
...  

Objective/Background and Aims. The gastrointestinal tract is rich in neurotransmitters, which play an essential role in the occurrence and development of gastrointestinal tumors. We aimed to explore the function of neurotransmitters in gastric cancer and identify a suitable target to treat gastric cancer patients in the future. Methods. Monoamine neurotransmitters were detected in gastric cancer tissue and paired normal tissue, and The Cancer Genome Atlas was used to identify differentially expressed norepinephrine-degrading and synthetic enzymes. Quantitative real-time PCR and the Seahorse assay were used to determine the effect of norepinephrine on gastric cancer cell glycolysis. MAOA expression in cancer tissues was analyzed by immunohistochemistry and was compared with the patient SUVmax value of PET-CT and other clinicopathological characteristics. Results. The norepinephrine levels were markedly high in gastric cancer tissue, while the norepinephrine-degrading enzymes MAOA and MAOB showed low expression. High norepinephrine levels were associated with activated glycolysis. The MAOA or MAOB expression levels in tumor tissue were closely correlated with the patient SUV max values of PET-CT and immunotherapy evaluation indices, such as PD-L1 and the microsatellite status. Conclusions. Norepinephrine shows relatively higher expression in gastric cancer tissue than in normal tissue, and its expression level is associated with the glycolysis levels in patients. The norepinephrine-degrading enzymes MAOA and MAOB have significant expression differences in cancer and normal tissue, and their missing or low expression may predict immune therapy outcomes for gastric cancer patients. High norepinephrine levels with metabolic abnormalities may be more suitable for metabolic targeted therapy or immunotherapy.


2021 ◽  
Vol 27 ◽  
Author(s):  
Sung Eun Oh ◽  
Mi Yun Oh ◽  
Ji Yeong An ◽  
Jun Ho Lee ◽  
Tae Sung Sohn ◽  
...  

Collagen is a major component in the tumor microenvironment. This study reveals a novel biomarker candidate, type VII collagen (COL7A1), in patients with gastric cancer. To identify genes differentially expressed in gastric cancer tissue, we analyzed cancerous (n = 20) and noncancerous tissues (n = 13) using a DNA microarray. To perform immunohistochemistry and validate the upregulation of COL7A1 expression, we collected 200 more gastric cancer tissues and 100 normal gastric tissues from 200 randomly selected patients who underwent gastrectomy for gastric cancer between January 2010 and December 2013. The correlations between COL7A1 expression and clinicopathological parameters and patients’ overall survival (OS) were analyzed. In the microarray, COL7A1 was upregulated in gastric cancer tissue compared with normal tissue. In the immunohistochemistry study, COL7A1 was more highly expressed in cancer tissue than in normal tissue (p = 0.001). Patients with intracellular COL7A1 expression had significantly poorer five-year OS than those with only extracellular expression (41.5 versus 69.7%, p = 0.001), and the site of expression was an independent prognostic factor of OS (hazard ratio 2.00, 95% CI 1.26–3.16, p = 0.003). Also, we found a significant association between the COL7A1 immunohistochemistry score and distant metastasis (high versus low, odds ratio 4.45, 95% CI 1.40–14.16, p = 0.011). The site and total immunohistochemistry score of COL7A1 expression in gastric cancer showed prognostic significance for OS and distant metastasis, respectively. COL7A1 could be a novel biomarker with diagnostic and therapeutic value.


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