The role of STEAP1 in the biological behavior of gastric cancer

2020 ◽  
Author(s):  
Zhe Zhang ◽  
Wen-bin Hou ◽  
Chao Zhang ◽  
Dong-dong Zhang ◽  
Wen An ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Protein Expression ◽  
Signaling Pathways ◽  
Rna Sequencing ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

Abstract Background: Six-transmembrane epithelial antigen 1 (STEAP1) is associated with the occurrence and development of cancer. This study aimed to clarify the role of STEAP1 in gastric cancer tumor growth and metastasis, as well as its molecular mechanism of action.Methods: Statistical methods were used for clinical data analysis. Protein expression was detected using immunohistochemistry. The mRNA and protein expression in the cell cultures were detected using reverse transcription-polymerase chain reaction and western blot analysis. Overexpression and silencing models were constructed using plasmid and lentivirus transfection. To detect cell proliferation in vitro, Cell Counting Kit-8, flow cytometry, and colony formation assays were used; transwell and wound healing assays were used to detect cell migration and invasion; RNA sequencing was used for identifying differentially expressed genes; ELISA assay was used to detect the secretory proteins in cells. For in vivo experiments, nude BALB/c mice were used for detecting subcutaneous tumorigenesis and intraperitoneal implantation.Results: STEAP1 was overexpressed in gastric cancer tissues and cell lines. Single factor and Cox analyses showed that STEAP1 gene expression level correlated with poor prognosis. Upregulation of STEAP1 increased cell proliferation, migration, and invasion, which decreased after STEAP1 was knocked down. These changes were achieved via the activation of the AKT/FoxO1 pathway and epithelial-mesenchymal transformation (EMT). The RNA sequencing results indicated that STEAP1 was closely related to inflammatory reactions. STEAP1 can regulate the inflammation-related molecules, IL-1β and IL-6, via the NF-kB and ERK/c-Jun signaling pathways. The in vivo animal experiments showed that STEAP1 knock down, resulted in a decrease in the subcutaneous tumor and peritoneal tumor formation.Conclusion: STEAP1 was overexpressed in gastric cancer and closely associated with OS. STEAP1 can regulate the cell cycle via the Akt/FoxO1 pathway to influence cell proliferation. STEAP1 may affect cell migration and invasion via EMT action. In addition, STEAP1 may mediate the inflammatory response by regulating IL1β and IL6 via the NF-kB and the ERK/c-Jun signaling pathways.

scholarly journals A Research of STEAP1 on the Biological Behavior of Gastric Cancer

2020 ◽  
Author(s):  
Zhe Zhang ◽  
Huimian Xu
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Protein Expression ◽  
Cell Counting ◽  
Biological Behavior ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Mesenchymal Transformation

Abstract Introduction:Six-Transmembrane Epithelial Antigene of the Prostate 1 (STEAP1) is associated with the occurrence and development of cancer. This study aimed to clarify the role of STEAP1 in gastric cancer tumor growth and metastasis, as well as its molecular mechanism of action. Methods：Statistical methods were used for clinical data analysis. Protein expression was detected using immunohistochemistry(IHC). The mRNA and protein expression in the cell cultures were detected using reverse transcription-polymerase chain reaction(RT-PCR) and western blot analysis. Overexpression and silencing models were constructed using plasmid and lentivirus transfection. To detect cell proliferation in vitro, Cell Counting Kit-8(CCK-8), flow cytometry, and colony formation assays were used; transwell and wound healing assays were used to detect cell migration and invasion; For in vivo experiments, nude BALB/c mice were used for detecting subcutaneous tumorigenesis and intraperitoneal implantation. Results：We found STEAP1 was overexpressed in gastric cancer tissues and cell lines. Single factor and Cox analyses showed that STEAP1 gene expression level correlated with poor prognosis. Upregulation of STEAP1 increased cell proliferation, migration, and invasion, which decreased after STEAP1 was knocked down. These changes were achieved via the activation of the AKT/FoxO1 pathway and epithelial-mesenchymal transformation (EMT). The in vivo animal experiments showed that STEAP1 knock down, resulted in a decrease in the subcutaneous tumor and peritoneal tumor formation.Conclusions：STEAP1 was overexpressed in gastric cancer and closely connected with OS. STEAP1 can regulate the cell cycle via the Akt/FoxO1 pathway to influence cell proliferation. STEAP1 may affect cell migration and invasion via EMT induction.

scholarly journals Acyl-CoA Synthetase 5 Promotes the Growth and Invasion of Colorectal Cancer Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Shihua Ding ◽  
Shaohui Tang ◽  
Min Wang ◽  
Donghai Wu ◽  
Haijian Guo
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Sw620 Cells ◽  
Role Of It

Background and Aims. Acyl-CoA synthetase 5 (ACS5) has been reported to be associated with the development of various cancers, but the role of it in colorectal cancer (CRC) is not well understood. The present study aimed to explore the potential role of ACS5 in the development and progression of CRC. Methods. ACS5 expression in CRC tissues and CRC cell lines was examined, and its clinical significance was analyzed. The role of ACS5 in cell proliferation, apoptosis, and invasion was examined in vitro. Results. We found that ACS5 expression was upregulated in CRC cells and CRC tissues and that high ACS5 expression was more frequent in CRC patients with excess muscular layer and with poor tumor differentiation. Furthermore, knockdown of ACS5 in HT29 and SW480 cells significantly dampened cell proliferation, induced cell apoptosis, and reduced cell migration and invasion. In contrast, the ectopic overexpression of ACS5 in LOVO and SW620 cells remarkably promoted cell proliferation, inhibited cell apoptosis, and enhanced cell migration and invasion. Enhanced cell growth and invasion ability mediated by the gain of ACS5 expression were associated with downregulation of caspase-3 and E-cadherin and upregulation of survivin and CD44. Conclusions. Our data demonstrate that ACS5 can promote the growth and invasion of CRC cells and provide a potential target for CRC gene therapy.

scholarly journals LncRNA TP73-AS1 down-regulates miR-139-3p to promote retinoblastoma cell proliferation

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhaoxia Xia ◽  
Xiaoxi Yang ◽  
Shuduan Wu ◽  
Zhizhen Feng ◽  
Lei Qu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Lines ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Retinoblastoma Cell ◽  
Non Coding Rnas ◽  
In Cells

Abstract Our study aimed to investigate the role of long non-coding RNAs (lncRNA) TP73-AS1 in retinoblastoma (Rb). In the present study, we found that TP73-AS1 was up-regulated, while miR-139–3p was down-regulated in Rb. TP73-AS1 and miR-139-3p were inversely correlated in Rb tissues. In cells of Rb cell lines, overexpression of miR-139-3p failed to affect TP73-AS1, while TP73-AS1 overexpression caused the down-regulated miR-139-3p. TP73-AS1 overexpression caused promoted proliferation of Rb cells but showed no significant effects on cell migration and invasion. miR-139-3p overexpression played an opposite role and attenuated the effects of TP73-AS1 overexpression. Therefore, lncRNA TP73-AS1 may down-regulate miR-139-3p to promote Rb cell proliferation.

scholarly journals miR-188-5p Suppresses Gastric Cancer Cell Proliferation and Invasion via Targeting ZFP91

2018 ◽  
Vol 27 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Yuping Peng ◽  
Xuning Shen ◽  
Honggang Jiang ◽  
Zhiheng Chen ◽  
Jiaming Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Inverse Correlation ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Promising Therapeutic Target ◽  
Cellular Apoptosis ◽  
Gastric Cancer Cell Proliferation

MicroRNAs (miRNAs) have been demonstrated to be essential regulators in the development and progression of various cancers. The role of miR-188-5p in gastric cancer (GC) has not been determined. In this study, we found that the expression of miR-188-5p was downregulated in GC tissues compared with adjacent normal tissues. The lowly expressed miR-188-5p was significantly associated with lymph node metastasis and advanced TNM stage. Moreover, overexpression of miR-188-5p significantly inhibited GC cell proliferation, migration, and invasion but promoted cellular apoptosis. Mechanistically, we identified transcription factor ZFP91 as a target gene of miR-188-5p in GC. We found that miR-188-5p overexpression significantly inhibited the expression of ZFP91 in GC cell lines. There was an inverse correlation between the expression of miR-188-5p and ZFP91 in GC tissues. We found that restoration of ZFP91 in miR-188-5p-overexpressed MGC-803 and SGC-7901 cells promoted cell proliferation, migration, and invasion. Finally, we also showed that overexpression of miR-188-5p inhibited tumor growth in vivo. Taken together, our findings indicated that miR-188-5p serves as a tumor suppressor in human GC by targeting ZFP91, suggesting that miR-188-5p might be a promising therapeutic target for GC treatment.

scholarly journals MECP2 promotes migration and invasion of gastric cancer cells via modulating the Notch1/c-Myc/mTOR signaling pathways by suppressing FBXW7 transcription

2020 ◽  
Author(s):  
Lingyu Zhao ◽  
Xiaofei Wang ◽  
Juan Yang ◽  
Qiuyu Jiang ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Mtor Signaling ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Gene Assay

Abstract Background: Methyl-CpG-binding protein 2 (MECP2), an epigenetic regulatory factor, promotes the carcinogenesis and progression of a number of cancers. However, its role in the migration and invasion of gastric cancer (GC) as well as the underlying molecular mechanisms remain unclear.Methods: Immunohistochemistry (IHC), Western blot, and quantitative real-time PCR (qRT-PCR) were performed to measure the expressions of MECP2, FBXW7, c-Myc, mTOR and Notch1 in GC tissues and cell lines, respectively. The effects of MECP2 silencing and overexpression on GC cell migration and invasion were detected by wound healing assay and transwell assay. The mechanisms of MECP2-mediated migration and invasion were further investigated using chromatin immunoprecipitation sequencing (ChIP-Seq) and luciferase reporter gene assay.Results: In this study, we found that MECP2 facilitated the migration and invasion of GC cells. Investigation of the molecular mechanism revealed that MECP2 restrained FBXW7 transcription in GC by binding to the methylated CpG sites of FBXW7’s promoter region. MECP2 expression was remarkably negatively correlated with the FBXW7 level in GC tissues. FBXW7 expression was significantly downregulated in GC tissues and cell lines, and low FBXW7 expression was correlated with the clinicopathologic features. FBXW7 repressed cell migration and invasion by regulating the Notch1/c-Myc/mTOR signaling pathways, and knockdown of FBXW7 reversed the effects of silencing MECP2. Moreover, MECP2 upregulated the Notch1/c-Myc/mTOR signaling pathways by inhibiting FBXW7 expression at the transcription level.Conclusion: This study demonstrates that MECP2 promotes migration and invasion of GC cells via modulating the Notch1/c-Myc/mTOR signaling pathways by suppressing FBXW7 transcription. The findings suggest that MECP2 may be a novel effective therapeutic target for GC patients.

scholarly journals Circ_MUC16 attenuates the effects of Propofol to promote the aggressive behaviors of ovarian cancer by mediating the miR-1182/S100B signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hao Yang ◽  
Yunrui Guo ◽  
Yecai Zhang ◽  
Decai Wang ◽  
Guoyun Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Lactate Production ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Aggressive Behaviors

Abstract Background Propofol is commonly used for anesthesia during surgery and has been demonstrated to inhibit cancer development, which is shown to be associated with deregulation of non-coding RNAs (ncRNAs). The objective of this study was to explore the role of circular RNA mucin 16 (circ_MUC16) in Propofol-mediated inhibition of ovarian cancer. Methods The expression of circ_MUC16, microRNA-1182 (miR-1182) and S100 calcium-binding protein B (S100B) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR). The expression of S100B protein was checked by western blot. Cell proliferation was assessed by 3-(4, 5-di methyl thiazol-2-yl)-2, 5-di phenyl tetrazolium bromide (MTT) assay and colony formation assay. Glycolysis metabolism was assessed by glucose consumption, lactate production and ATP level. Cell migration and cell invasion were assessed by transwell assay. Cell migration was also assessed by wound healing assay. Animal study was conducted in nude mice to determine the role of circ_MUC16 in vivo. The relationship between miR-1182 and circ_MUC16 or S100B was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results Propofol inhibited ovarian cancer cell proliferation, glycolysis metabolism, migration and invasion, which were partly recovered by circ_MUC16 overexpression. Circ_MUC16 was downregulated in Propofol-treated ovarian cancer cells. Besides, circ_MUC16 knockdown enhanced the effects of Propofol to further inhibit tumor growth in vivo. MiR-1182 was a target of circ_MUC16, and circ_MUC16 knockdown-inhibited cell proliferation, glycolysis metabolism, migration and invasion were partly restored by miR-1182 inhibition. In addition, S100B was a target of miR-1182, and miR-1182-suppressed cell proliferation, glycolysis metabolism, migration and invasion were partly restored by S100B overexpression. Conclusion Circ_MUC16 overexpression alleviated the effects of Propofol to promote the aggressive behaviors of ovarian cancer by targeting the miR-1182/S100B network.

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 Exosomal miR-126 blocks the development of non-small cell lung cancer through the inhibition of ITGA6

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Mingjun Li ◽  
Qianqian Wang ◽  
Xiaofei Zhang ◽  
Ningning Yan ◽  
Xingya Li
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Tumor Growth ◽  
Western Blot ◽  
Colony Formation ◽  
Nsclc Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

Abstract Background Exosomes, emerging mediators of intercellular communication, are reported to transfer certain non-coding RNAs, such as microRNAs (miRNAs), which play a crucial role in cancer progression. The objective of this study was to determine the function of exosomal miR-126 and provide a novel mechanism of miR-126 action in NSCLC. Methods The morphology of exosomes was identified by transmission electron microscope (TEM), and the exosomal surface markers were quantified by western blot. The expression of miR-126 and integrin alpha-6 (ITGA6) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR), and ITGA6 protein expression was determined by western blot. For functional analyses, cell proliferation was assessed by colony formation assay and MTT assay. Cell cycle and cell apoptosis were monitored using flow cytometry assay. Cell migration and invasion were determined by transwell assay. ITGA6 was predicted as a target of miR-126 by bioinformatics analysis, which was verified by dual-luciferase reporter assay. The role of exosomal miR-126 in vivo was determined by Xenograft tumor models. Results NSCLC serum-derived exosomes harbored low expression of miR-126 and promoted NSCLC cell proliferation, cell cycle progression, cell migration and invasion. NSCLC serum-derived exosomes loaded with miR-126 mimic inhibits NSCLC cell proliferation, colony formation, migration and invasion but induced cell cycle arrest and apoptosis. Besides, exosomal miR-126 also blocked tumor growth in vivo. In mechanism, ITGA6 was a target of miR-126, and exosomal miR-126 weakened these NSCLC cell malignant behaviors and inhibited tumor growth by degrading the expression of ITGA6. Conclusion Exosomal miR-126 blocked the progression of NSCLC through the mediation of its target gene ITGA6, and exosomal miR-126 might be used as a promising biomarker for NSCLC therapy.

scholarly journals Arsenic sulfide inhibits cell migration and invasion of gastric cancer in vitro and in vivo

2015 ◽  
pp. 5579 ◽  
Author(s):  
Siyu Chen ◽  
Lian Zhang ◽  
Sungkyoung Kim ◽  
Wenping Ding ◽  
Yingying Tong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Migration And Invasion ◽  
Arsenic Sulfide ◽  
Cell Migration And Invasion

scholarly journals DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3463
Author(s):  
Sheng-Fan Wang ◽  
Kuo-Hung Huang ◽  
Wei-Chuan Tseng ◽  
Jeng-Fan Lo ◽  
Anna Fen-Yau Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion ◽  
Gastric Cancers ◽  
Gastric Cancer Patients

Background: Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated. Methods: The clinical TCGA online database and immunohistochemical staining for Tid1 expression in tumor samples of gastric cancer patients were analyzed. Tid1 knockdown by siRNA was applied to investigate the role of Tid1 in gastric cancer cells. Results: Low Tid1 protein-expressing gastric cancer patients had a poorer prognosis and higher lymph node invasion than high Tid1-expressing patients. Knockdown of Tid1 did not increase cell proliferation, colony/tumor sphere formation, or chemotherapy resistance in gastric cancer cells. However, Tid1 knockdown increased cell migration and invasion. Moreover, Tid1 knockdown reduced the mtDNA copy number of gastric cancer cells. In addition, the Tid1-galectin-7-MMP-9 axis might be associated with Tid1 knockdown–induced cell migration and invasion of gastric cancer cells. Conclusions: Tid1 is required for mtDNA maintenance and regulates migration and invasion of gastric cancer cells. Tid1 deletion may be a poor prognostic factor in gastric cancers and could be further investigated for development of gastric cancer treatments.

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