scholarly journals BAP-1 Inhibits Gastric Cancer Progression via PI3K/AKT Pathway by Suppressing FOXK1 Expression

2021 ◽  
Author(s):  
Chen Mi ◽  
Yan Zhao ◽  
Li Ren ◽  
Dan Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Ags Cells ◽  
Mesenchymal Transition

Abstract BRCA1-Associated Protein-1 (BAP-1) gene functions as a vital mediator in tumor formation, progression, and metastasis. The involvement of BAP-1 in colon cancer has been widely reported, but the role of BAP-1 in gastric cancer (GC) is still unclear. In this study, we sought to investigate the contribution of BAP-1 in the pathogenesis of GC. qPCR and Western blot assay were used to detect the mRNA and protein expression of BAP-1 in GC cell lines. MTT and transwell assay were employed to determine the cell viability, migration, and invasion. Annexin V-PI double staining was used to evaluate cell apoptosis. We reported that BAP-1 was expressed at a low level in GC cell lines. Overexpression of BAP-1 inhibited cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) and promoted apoptosis in HGC-27 and AGS cells. BAP-1 inactivated the PI3K/AKT pathway by suppressing Forkhead-box K1 (FOXK1) expression. Moreover, overexpression of FOXK1 reversed the effect of BAP-1 on cell viability, apoptosis, migration, invasion, and EMT. Our data revealed that BAP-1 inhibits cell viability, migration, invasion, and EMT process and promoted apoptosis in HGC-27 and AGS cells through PI3K/AKT pathway via suppressing FOXK1 expression. Thus, BAP-1 can serve as a potential therapeutic target in GC treatment.

scholarly journals MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

2009 ◽  
Vol 20 (24) ◽  
pp. 5127-5137 ◽  
Author(s):  
Kai-Wen Hsu ◽  
Rong-Hong Hsieh ◽  
Chew-Wun Wu ◽  
Chin-Wen Chi ◽  
Yan-Hwa Wu Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Suppressive Effect ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Cox 2

The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1 knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1-suppressed tumor progression in SC-M1 cells were through inhibition of COX-2 expression. MBP-1 also exerted a suppressive effect on tumor progression of other gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results suggest that MBP-1–suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer.

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.

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.

SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer

2020 ◽  
Author(s):  
Sisi Wei ◽  
Shiping Sun ◽  
Xinliang Zhou ◽  
Cong Zhang ◽  
Xiaoya Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Underlying Mechanisms ◽  
And Function

Abstract A substantial fraction of transcripts are known as long noncoding RNAs (lncRNAs), and these transcripts play pivotal roles in the development of cancer. However, little information has been published regarding the functions of lncRNAs in oesophageal squamous cell carcinoma (ESCC) and the underlying mechanisms. In our previous studies, we demonstrated that small nucleolar RNA host gene 5 (SNHG5), a known lncRNA, is dysregulated in gastric cancer (GC). In this study, we explored the expression and function of SNHG5 in development of ESCC. SNHG5 was found to be downregulated in human ESCC tissues and cell lines, and this downregulation was associated with cancer progression, clinical outcomes and survival rates of ESCC patients. Furthermore, we also found that overexpression of SNHG5 significantly inhibited the proliferation, migration and invasion of ESCC cells in vivo and in vitro. Notably, we found that metastasis-associated protein 2 (MTA2) was pulled down by SNHG5 in ESCC cells using RNA pulldown assay. We also found that SNHG5 reversed the epithelial–mesenchymal transition by interacting with MTA2. In addition, overexpression of SNHG5 downregulated the transcription of MTA2 and caused its ubiquitin-mediated degradation. Thus, overexpression of MTA2 partially abrogated the effect of SNHG5 in ESCC cell lines. Furthermore, we found that MTA2 mRNA expression was significantly elevated in ESCC specimens, and a negative correlation between SNHG5 and MTA2 expression was detected. Overall, this study demonstrated, for the first time, that SNHG5-regulated MTA2 functions as an important player in the progression of ESCC and provide a new potential therapeutic strategy for ESCC.

scholarly journals Adenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K–AKT–mTOR signaling

2019 ◽  
Vol 30 (19) ◽  
pp. 2527-2534 ◽  
Author(s):  
Linsen Shi ◽  
Zhaoying Wu ◽  
Ji Miao ◽  
Shangce Du ◽  
Shichao Ai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Mesenchymal Transition ◽  
Poor Outcomes

The accumulation of adenosine in the tumor microenvironment is associated with tumor progression in many cancers. However, whether adenosine is involved in gastric cancer (GC) metastasis and progression, and the underlying molecular mechanism, is largely unclear. In this study, we find that GC tissues and cell lines had higher A2aR levels than nontumor gastric tissues and cell lines. A2aR expression correlated positively with TNMstage, and associated with poor outcomes. Adenosine enhanced the expression of the stemness and epithelial–mesenchymal transition-associated genes by binding to A2aR. A2aR expression on GC cells promoted metastasis in vivo. The PI3K-AKT-mTOR signaling pathway was involved in adenosine-stimulated GC cell migration and invasion. Our results indicate that adenosine promotes GC cell invasion and metastasis by interacting with A2aR to enhance PI3K–AKT–mTOR pathway signaling.

scholarly journals A transcription factor that promotes proliferation, migration, invasion, and epithelial–mesenchymal transition of ovarian cancer cells and its possible mechanisms

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yingying Qi ◽  
Kexin Mo ◽  
Ting Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
High Morbidity ◽  
Mesenchymal Transition ◽  
Gata3 Expression

Abstract Background Ovarian cancer is one of the most common gynecological malignancies with the high morbidity and mortality. This study was aimed to explore the role of non-structure maintenance of chromosomes condensin I complex subunit H (NCAPH) in the progression of ovarian cancer (OC) and the transcription regulatory effects of GATA binding protein 3 (GATA3) on this gene. Methods Firstly, NCAPH and GATA3 expression in OC tissues and several human OC cell lines was, respectively, evaluated by TNMplot database and Western blot analysis. Then, NCAPH was silenced to assess the proliferation, migration, and invasion of OC cells in turn using CCK-8, wound healing, and transwell assays. Western blotting was used to determine the expression of epithelial--mesenchymal transition (EMT)-related proteins and PI3K/PDK1/AKT signaling proteins. The potential binding sites of GATA3 on NCAPH promoter were predicated using JASPAR database, which were verified by luciferase reporter assay and chromosomal immunoprecipitation. Subsequently, GATA3 was overexpressed to examine the biological functions of OC cells with NCAPH silencing. Results NCAPH and GATA3 expression was significantly upregulated in OC tissues and cell lines. NCAPH loss-of-function notably inhibited the proliferation, migration, invasion, and EMT of OC cells. Moreover, the expression of p-PI3K, PDK1, and p-AKT was downregulated after NCAPH knockdown. Furthermore, GATA3 was confirmed to bind to NCAPH promoter. GATA3 overexpression alleviated the inhibitory effects of NCAPH silencing on the proliferation, migration, invasion, EMT, and expression of proteins in PI3K/PDK1/AKT pathway of OC cells. Conclusion To sum up, NCAPH expression transcriptional activation by GATA3 accelerates the progression of OC via upregulating PI3K/PDK1/AKT pathway.

scholarly journals Circular RNA circFGD4 suppresses gastric cancer progression via modulating miR-532-3p/APC/β-catenin signalling pathway

2020 ◽  
Author(s):  
Xinglong Dai ◽  
Jianjun Liu ◽  
Xiong Guo ◽  
Anqi Cheng ◽  
Xiaoya Deng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Potential Biomarker

Background: Mounting evidence has displayed critical roles of circular RNAs (circRNAs) in multiple cancers. The underlying mechanisms by which circFGD4 contributed to gastric cancer (GC) are still unclear. Methods: The levels and clinical values of circFGD4 in GC patients were detected and analysed by quantitative real-time PCR. The biological roles of circFGD4 in GC were assessed in vitro and in vivo experiments. Dual-luciferase reporter, fluorescence in situ hybridization, RNA immunoprecipitation, biotin-coupled RNA pull-down, and TOP/Flash and FOP/Flash reporter gene assays were employed to evaluate the effects of circFGD4 on miR-532-3p-mediated adenomatous polyposis coli (APC)/β-catenin signalling in GC cells. Results: circFGD4 expression was down-regulated the most in human GC tissues and cell lines. Low expression of circFGD4 was correlated with poor tumour differentiation, lymphatic metastasis, and poor prognosis of GC patients. circFGD4 suppressed GC cell viability, colony formation, migration, induced epithelial-mesenchymal transition (EMT) and tumorigenesis and metastasis in vivo. Next, we validated that circFGD4 acted as a sponge of miR-532-3p to relieve the tumour-promoting effects of miR-532-3p on its target APC. The mechanistic analysis demonstrated that the circFGD4 suppressed GC cell viability, migration, and EMT by modulating the miR-532-3p/APC axis to inactivate the β-catenin signalling. Conclusion: circFGD4 suppressed GC progression through sponging miR-532-3p and enhancing APC expression to inactivate the β-catenin signalling. Thus circFGD4 provides a novel potential biomarker and valuable therapeutic strategy for GC.

Melittin suppresses epithelial–mesenchymal transition and metastasis in human gastric cancer AGS cells via regulating Wnt/BMP associated pathway

2021 ◽  
Author(s):  
Jye-Yu Huang ◽  
Shu-Fen Peng ◽  
Fu-Shin Chueh ◽  
Po-Yuan Chen ◽  
Yi-Ping Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

ABSTRACT Gastric cancer has a poor prognosis; once cancer has metastasized, it can easily lead to patient death. Melittin is one of the major components extracted from the bee venom. It has been shown that melittin emerges antitumor activities against many human cancer cell lines. Our results indicated that melittin at 0.2-0.5 µm significantly reduced total cell viability in human gastric cancer AGS cells. At low concentrations (0.05-0.15 µm), melittin displayed antimetastasis effects and inhibited cell adhesion and colony formation. Besides, it inhibited cell motility and suppressed cell migration and invasion. Melittin inhibited the activities of MMP-2 and MMP-9 and the integrity of cell membrane in AGS cells. Furthermore, Western blotting results showed that melittin decreased the protein expressions of Wnt/BMP and MMP-2 signaling pathways. Based on these observations, melittin inhibited cell migration and invasion of AGS cells through multiple signaling pathways. It may be used to treat metastasized gastric cancers in the future.

scholarly journals Knockdown of TPT1-AS1 inhibits cell proliferation, cell cycle G1/S transition, and epithelial–mesenchymal transition in gastric cancer

2020 ◽  
Author(s):  
Jun Tang ◽  
Fei Huang ◽  
Hui Wang ◽  
Feng Cheng ◽  
Yaping Pi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Epithelial Mesenchymal Transition ◽  
Negative Control ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Normal Tissues

Long non-coding RNAs are considered to be critical regulators of tumor progression. Tumor protein translationally controlled 1 antisense RNA 1 (TPT1-AS1) was shown to have an oncogenic role in cervical and ovarian cancer. The clinical significance and biological function of TPT1-AS1 in gastric cancer (GC) are not clear. In this study, we analyzed the expression of TPT1-AS1 in GC tissues and cell lines and performed functional and mechanistic analysis of TPT1-AS1 effects on GC cell proliferation, migration, and invasion. TPT1-AS1 expression was determined in 76 pairs of GC tissues vs. matched adjacent normal tissues and in four GC cell lines (SGC-7901, AGS, BGC-823, and MGC-803) vs. GES-1 cell line by quantitative reverse transcription PCR. SGC-7901 and MGC-803 cells were transfected with small interfering RNA or scrambled negative control, and cell proliferation, colony formation, migration, invasion and cell cycle assays were performed. The expression of proteins involved in cell cycle progression and epithelial–mesenchymal transition was analyzed by Western blot. TPT1-AS1 expression was significantly higher in GC tissues and cell lines compared to controls. The overexpression of TPT1-AS1 was significantly correlated with TNM stage and lymph node metastasis, and it was associated with worse prognosis of GC patients according to the Kaplan–Meier survival analysis and Cox proportional hazard regression analysis. The knockdown of TPT1-AS1 significantly inhibited proliferation, cell cycle G1/S transition, migration, and invasion of SGC-7901 and MGC-803 cells. Moreover, TPT1-AS1 knockdown downregulated the expression of CDK4, cyclin D1, and vimentin and upregulated the expression of p21 and E-cadherin. Our findings suggest that TPT1-AS1 may be a promising therapeutic target in GC.

scholarly journals MiR-877 suppresses gastric cancer progression by downregulating AQP3

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052090366 ◽  
Author(s):  
Hongyu Zhu ◽  
Yulian Wu ◽  
Muxing Kang ◽  
Bo Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Reporter Assays

Objectives Gastric cancer (GC) is the leading cause of cancer-related deaths worldwide; however, the underlying molecular mechanisms of GC remain unclear. This study investigated the role of the miR-877–AQP3 axis in GC tumorigenesis. Methods The levels of miR-877 expression were measured in GC tissues and cell lines by qRT-PCR. Functional assays were performed to elucidate the role of miR-877 in GC development. Results Our results showed that miR-877 levels were lower in GC tissues and cell lines compared with the corresponding controls. Additionally, reduced miR-877 levels were associated with unfavorable prognoses. Increased miR-877 expression suppressed proliferation, invasion, and epithelial-mesenchymal transition, while promoting apoptosis in GC cells. Luciferase reporter assays showed that aquaporin 3 (AQP3) was a direct downstream target of miR-877. Overexpression of AQP3 partially rescued the tumor suppressive effects of miR-877 in GC cells. Moreover, miR-877 was negatively correlated with AQP3 mRNA expression in GC tissues. Conclusions This study demonstrated that miR-877 plays a suppressive role in GC tumorigenesis by regulating AQP3.

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