scholarly journals Silencing of Long Non-coding RNA HOTAIR Suppresses Reverses Epithelial-Mesenchymal Transition in AGS Gastric Cancer Cell Line by Downregulation of Fibronectin 1 and Claudin-4

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Pegah Babapour ◽  
Maryam Tahmasebi-Birgani ◽  
Mehrdad Hashemi ◽  
Mohammad-Reza Hajjari
Keyword(s):  
Gastric Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Gastric Cancer Cell Line ◽  
P Value ◽  
Ags Cells ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Human Cancers

Background: Gastric cancer is the second reason for cancer mortality worldwide, with a high capacity for metastasis. Long non-coding RNAs (lncRNAs) are recently described as lengthy transcripts with no open reading frame. The lncRNAs play an important role in critical cellular and molecular pathways, including cell cycle, growth, differentiation, and apoptosis. Therefore, it is not surprising that abnormal expression of lncRNAs may be involved in human cancers. The HOX antisense intergenic RNA (HOTAIR) is a highly cited lncRNAs whose altered expression has been reported in a variety of human cancers such as gastric cancer. Epithelial to mesenchymal transition (EMT) is a cellular route in which an epithelial phenotype of the cells can be changed into the mesenchymal state. The signaling pathways involved in EMT are related to cancer metastasis and recurrence of gastric cancer. Methods: The present study aimed to investigate the effect of HOTAIR gene silencing on expression levels of fibronectin 1 (FN1) and claudin-4 (CLDN4) genes, two important markers of EMT, in AGS cellular model of gastric cancer. The AGS cells were exposed to the HOTAIR-specific siRNA for 48 hours. The extracted RNAs were subjected to complementary DNA synthesis and real-time PCR. Data were analyzed using 2−ΔΔCt method. Cells with no siRNA treatment were considered control set. The P-value < 0.05 was considered statistically significant. Results: The observed data showed that the expression levels of two EMT markers FN1 and CLDN4, were significantly decreased after HOTAIR silencing. Conclusions: This study demonstrates that HOTAIR can regulate the EMT signaling pathway through critical EMT factors like FN1 and CLDN4 transcripts. However, a long way remains to apply this finding in therapeutic approach, and further experiments are needed.

scholarly journals Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

2017 ◽  
Vol 42 (3) ◽  
pp. 1025-1036 ◽  
Author(s):  
Dehu Chen ◽  
Guiyuan Liu ◽  
Ning Xu ◽  
Xiaolan You ◽  
Haihua Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Ags Cells ◽  
Mesenchymal Transition

Background/Aims: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

The Effect of Dihydroartemisinin on the Malignancy and Epithelial-Mesenchymal Transition of Gastric Cancer Cells

2019 ◽  
Vol 20 (9) ◽  
pp. 719-726 ◽  
Author(s):  
Nan Li ◽  
Suyun Zhang ◽  
Qiong Luo ◽  
Fang Yuan ◽  
Rui Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Expression Levels

Objective: This study aimed to observe the effects of dihydroartemisinin (DHA) on the proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) of the human gastric cancer cell line SGC7901 cultured in vitro. Methods: We applied varying concentrations of DHA to SGC7901 cells. Cell proliferation was measured using the cell counting kit-8 (CCK-8). Flow cytometry, Transwell invasion assay, and cell scratch assay were used to investigate the cells’ apoptosis, invasion, and migration. Western blot was used to assess the expression levels of EMT markers E-cadhein and Vimentin, protein kinases Akt and phosphorylated AKT (p-AKT), and the cell transcription factor Snail. Results: DHA can effectively inhibit the malignant proliferation of gastric cancer cells in a time- and dose-dependent manner. In this study, with longer incubation times and increased drug concentrations, the antiproliferation effect of DHA on SGC7901 cells increased gradually (P<0.05). In addition, with the increase of drug concentration, the expression levels of E-cadhein, an epithelial-mesenchymal transition marker, remarkably increased, whereas the protein expression levels of the mesenchymal markers Vimentin, Akt, p-Akt, and Snail significantly decreased (P<0.05). Conclusion: DHA can effectively inhibit the proliferation, invasion, and metastasis of the gastric cancer cell line SGC7901 and induce cancer cell apoptosis. DHA can also downregulate PI3K/AKT and Snail activities and inhibit the epithelial-mesenchymal transition of gastric cancer cells. The potential anticancer effects of DHA deserve further investigation.

scholarly journals Entrectinib Induces Apoptosis and Inhibits the Epithelial–Mesenchymal Transition in Gastric Cancer with NTRK Overexpression

2021 ◽  
Vol 23 (1) ◽  
pp. 395
Author(s):  
Sung-Hwa Sohn ◽  
Hee Jung Sul ◽  
Bum Jun Kim ◽  
Hyeong Su Kim ◽  
Dae Young Zang
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
High Expression ◽  
Mechanistic Study ◽  
Sequencing Analysis ◽  
Receptor Kinase ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Gastric Cancer Patients

Tropomyosin receptor kinase (TRK) and receptor tyrosine kinase (RTK class VII) expression are important in many human diseases, especially cancers, including colorectal, lung, and gastric cancer. Using RNA sequencing analysis, we evaluated the mRNA expression and mutation profiles of gastric cancer patients with neurotropic tropomyosin receptor kinase (NTRK) 1-3 overexpression (defined as a ≥2.0-fold change). Furthermore, we screened eight TRK inhibitors in NCI-N87, SNU16, MKN28, MKN7, and AGS cells. Among these inhibitors, entrectinib showed the highest inhibitory activity; therefore, this drug was selected for analysis of its therapeutic mechanisms in gastric cancer. Entrectinib treatment induced apoptosis in NTRK1-3-expressing and VEGFR2-expressing NCI-N87 and AGS cells, but it had no effect on NTRK1-3-, VEGFR2-, TGFBR1-, and CD274-expressing MKN7 cells. SNU16 and MKN28 cells with low NTRK1-3 expression were not affected by entrectinib. Therefore, a mechanistic study was conducted in NCI-N87 (high expression of NTRK1-3 but mutation of NTRK3), AGS (high expression of NTRK1-3) and MKN28 (low expression of NTRK1-3) gastric cancer cell lines. Entrectinib treatment significantly reduced expression levels of phosphorylated NFκB, AKT, ERK, and β-catenin in NCI-N87 and AGS cells, whereas it upregulated the expression levels of ECAD in NCI-N87 cells. Together, these results suggest that entrectinib has anti-cancer activity not only in GC cells overexpressing pan NTRK but also in VEGFR2 GC cells via the inhibition of the pan NTRK and VEGFR signaling pathways.

scholarly journals CD36 promotes the epithelial–mesenchymal transition and metastasis in cervical cancer by interacting with TGF-β

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Min Deng ◽  
Xiaodong Cai ◽  
Ling Long ◽  
Linying Xie ◽  
Hongmei Ma ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Cd36 Expression ◽  
Cervical Cancer Cells

Abstract Background Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer. Methods Using immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters. The effect of CD36 expression on the epithelial–mesenchymal transition (EMT) in cervical cancer cells was evaluated by Western immunoblotting analysis. In vitro invasion and in vivo metastasis assays were also used to evaluate the role of CD36 in cervical cancer metastasis. Results In the present study, we confirmed that CD36 was highly expressed in cervical cancer samples relative to normal cervical tissues. Moreover, overexpression of CD36 promoted invasiveness and metastasis of cervical cancer cells in vitro and in vivo, while CD36 knockdown suppressed proliferation, migration, and invasiveness. We demonstrated that TGF-β treatment attenuated E-cadherin expression and enhanced the expression levels of CD36, vimentin, slug, snail, and twist in si-SiHa, si-HeLa, and C33a–CD36 cells, suggesting that TGF-β synergized with CD36 on EMT via active CD36 expression. We also observed that the expression levels of TGF-β in si-SiHa cells and si-HeLa cells were down-regulated, whereas the expression levels of TGF-β were up-regulated in C33a–CD36 cells. These results imply that CD36 and TGF-β interact with each other to promote the EMT in cervical cancer. Conclusions Our findings suggest that CD36 is likely to be an effective target for guiding individualized clinical therapy of cervical cancer.

scholarly journals CLIC4 abrogation promotes epithelial–mesenchymal transition in gastric cancer

2019 ◽  
Vol 41 (6) ◽  
pp. 841-849 ◽  
Author(s):  
Baolong Wang ◽  
Jiqing Zheng ◽  
Qiongyuan Chen ◽  
Chaofan Wu ◽  
Yangxin Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Stage ◽  
Stem Cell Markers ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Cancer Stem Cell Markers ◽  
Normal Tissues ◽  
Gastric Adenocarcinomas ◽  
Etoposide Treatment

Abstract Chloride intracellular channel protein 4 (CLIC4) has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by western blot and real-time PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared with adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells, which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared with N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44 and OCT4, and inhibited migration, invasion and epithelial–mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.

scholarly journals High-Throughput Screening Identifies miR-451 as a Pleiotropic Modulator That Suppresses Gastric Cancer Metastasis

2016 ◽  
Vol 22 (2) ◽  
pp. 136-143 ◽  
Author(s):  
Wendao You ◽  
Liang Xu ◽  
Xing Zhang ◽  
Huan Zou ◽  
Dongtao Shi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
High Throughput Screening ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Human Gastric Cancer ◽  
Mesenchymal Transition ◽  
Therapeutic Uses ◽  
Human Carcinomas ◽  
Insight Into

MicroRNAs (miRNAs) are globally dysregulated in human carcinomas. However, the specific miRNAs that mediate gastric cancer metastasis have not been identified. We identified 100 miRNAs that are dysregulated in gastric cancer and used a self-assembled cell microarray method to systematically evaluate their capacity to regulate cell migration. MiR-451, which is down-regulated in human gastric cancer samples, potently modulated multiple metastatic phenotypes including cell migration, invasion, proliferation, and epithelial-mesenchymal transition. These effects were achieved via down-regulation of the miR-451 target gene, ERK2. These findings provide new insight into the physiological effects of and potential therapeutic uses for miRNAs in gastric cancer.

scholarly journals WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

2016 ◽  
Vol 39 (6) ◽  
pp. 2149-2157 ◽  
Author(s):  
Xiangshu Xian ◽  
Liuye Huang ◽  
Bo Zhang ◽  
Chengrong Wu ◽  
Jun Cui ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cannabis Sativa ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Active Components ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Cox 2

Background: Cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis. Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN) was associated with gastric cancer (GC) metastasis, but the mechanisms were unknown. Methods: The effects of WIN on GC cell migration and invasion were analyzed by the wound-healing assay and Transwell assay. Quantitative real-time PCR and Western blot were used to evaluate changes in expression of COX-2 and EMT associated markers in SGC7901 and AGS cells. Results: WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT) in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2) expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells. Conclusion: WIN can inhibit the EMT of GC cells through the downregulation of COX-2.

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