RACK1 to modulate expression of MMP10 via Src/NF-κB pathway in gastric cancer.

e15529 Background: Receptor of activated C kinase 1 (RACK1) is regarded as a scaffolding protein in multiple intracellular signal transduction pathways. Our previous works had demonstrated that RACK1 might involve in progression of gastric cancer, and could be a criterion to predict the good prognosis for the patients after surgical resection. The aim of this study is to explore the regulatory role of RACK1 in matrix metalloproteinase 10 (MMP10) autocrine, and which may be involved in invasion of gastric cancer. Methods: RACK1 knockdown gastric cell lines were established by shRNA. Secretion of cytokines secretion, as well as MMP10 was measured by antibody arrays and enzyme-linked immunosorbent assay. Cell migration and invasion was compared between normal and RACK1 knockdown cells. Pharmacological inhibitors were employed in searching specific signaling pathway. The correlation of RACK1 and MMP10 expression in gastric cancer samples was analyzed by Spearman’s ρ test. Results: Expression of MMP10 was substantially enhanced after knockdown of RACK1 in vitro, which contributed to enhanced migration and invasiveness of gastric cancer cells in autocrine manner. Specific inhibitors of NF-κB and c-Src, as well as overexpression of dominant-negative c-Src mutant, could suppress the expression of MMP10. Finally, an inverse correlation of RACK1 and IL-8 expression was confirmed in gastric cancer samples. Conclusions: Down-regulation of RACK1 resulted in the up-regulation of MMP10 in gastric cancer, which might enhance invasiveness via Src/NF-κB pathway partially.

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Silencing of hsa_circ_0000515 Inhibits Proliferation, Migration and Invasion of Gastric Cancer Cells by Sponging miR-615-5p In Vitro

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2733 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1466-1476

Author(s):

Xuli Wang ◽

Aiping Wang

Keyword(s):

Gastric Cancer ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Pcr Analysis ◽

Circular Rnas ◽

Loss Of Function ◽

Gastric Cancer Cells ◽

Novel Target

Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. This study investigates the role of circRNA hsa_circ_0000515 in gastric cancer (GC) cells and the underlying mechanism associated with microRNA-615-5p (miR-615-5p). qRT-PCR analysis showed the upregulation of hsa_circ_0000515 and downregulation of miR-615-5p in GC cell lines. Loss-of-function experiments indicated that suppression of hsa_circ_0000515 inhibited cell proliferation, migration, and invasion. Dual-luciferase reporter assay highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-615-5p. Furthermore, hsa_circ_0000515 could interact with splicing factors and bind miR-615-5p to regulate progression of GC cells. Deficiency of miR-615-5p reverses the inhibitory roles of si-hsa_circ_0000515 on the proliferation, migration, and invasion of GC cells. The findings highlighted the promising uses of hsa_circ_0000515 as a likely novel target for gastric cancer treatment.

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Has-miR-875-5p Inhibits Tumorigenesis by Targeting USF2 via TGF-β Signaling Pathway in Gastric Cancer

10.21203/rs.3.rs-885737/v1 ◽

2021 ◽

Author(s):

Shenshuo Gao ◽

Zhikai Zhang ◽

Xubin Wang ◽

Yan Ma ◽

Chensheng Li ◽

...

Keyword(s):

Gastric Cancer ◽

Signaling Pathway ◽

Research Direction ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

New Research

Abstract Background: Gastric cancer (GC) is one of the most common malignancies, and more and more evdiences show that the pathogenesis is regulated by various miRNAs.In this study, we investigated the role of miR-875 in GC. Methods:The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA RT-PCR. The effect of miR-875-5p on GC proliferation was determined by CCK-8 proliferation assay and EDU assay. Migration and invasion were examined by transwell migration and invasion assay and wound healing assay. The interaction between miR-875-5p and its target gene USF2 was verified by a dual luciferase reporter assay. The effects of miR-875-5p in vivo were studied in xenograft nude mice models.Related proteins were detected by Western blot.Results:The results showed that miR-875-5p inhibited the proliferation, migration and invasion of gastric cancer cells in vitro, and inhibited tumorigenesis in vivo. USF2 proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracts the effects of miR-875-5p inhibitors.Overexpression of miR-875-5p can inhibit proliferation, migration, and invasion through the TGF-β signaling pathway by down-regulation of USF2 in GC, providing a new research direction for the diagnosis and targeted therapy of GC.Conclusions: MiR-875-5pcan inhibited the progression of GC by directly targeting USF2 and negatively regulating TGF-β signaling pathway.In the future, miR-875-5p is expected to be used as a potential therapeutic target for GC therapy.

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Downregulation of CCKBR Expression Inhibits the Proliferation of Gastric Cancer Cells, Revealing a Potential Target for Immunotoxin Therapy

Current Cancer Drug Targets ◽

10.2174/1568009622666220106113616 ◽

2022 ◽

Vol 22 ◽

Author(s):

Meng Li ◽

Jiang Chang ◽

Honglin Ren ◽

Defeng Song ◽

Jian Guo ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Counting ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Aberrant Expression ◽

Promising Target ◽

The Impact

Background Increased CCKBR expression density or frequency has been reported in many neoplasms. Objective We aimed to investigate whether CCKBR drives the growth of gastric cancer (GC) and its potential as a therapeutic target of immunotoxins. Methods A lentiviral interference system was used to generate CCKBR-knockdown gastric cancer cells. Cell Counting Kit-8 and clonogenic assays were used to evaluate cell proliferation. Wound-healing and cell invasion assays were performed to evaluate cell mobility. Cell cycle was analyzed by flow cytometry. Tumor growth in vivo was investigated using a heterologous tumor transplantation model in nude mice. In addition, we generated the immunotoxin FQ17P and evaluated the combining capacity and tumor cytotoxicity of FQ17P in vitro. Results Stable downregulation of CCKBR expression resulted in reduced proliferation, migration and invasion of BGC-823 and SGC-7901 cells. The impact of CCKBR on gastric cancer cells was further verified through CCKBR overexpression studies. Downregulation of CCKBR expression also inhibited the growth of gastric tumors in vivo. Furthermore, FQ17P killed CCKBR-overexpressing GC cells by specifically binding to CCKBR on the tumor cell surface. Conclusion The CCKBR protein drives the growth, migration, and invasion of gastric cancer cells, and it might be a promising target for immunotoxin therapy based on its aberrant expression, functional binding interactions with gastrin, and subsequent internalization.

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Upregulated Vav2 in gastric cancer tissues promotes tumor invasion and metastasis

Tumor Biology ◽

10.1177/1010428317698392 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831769839 ◽

Cited By ~ 5

Author(s):

Bi-bo Tan ◽

Yong Li ◽

Li-qiao Fan ◽

Qun Zhao ◽

Qing-wei Liu ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Activity ◽

Migration And Invasion ◽

Invasion And Metastasis ◽

Clinical Value ◽

Gastric Cancer Cells ◽

Positive Rate ◽

Cancer Tissues ◽

The Relationship

Several studies have proved that Vav2 gene is associated with the carcinogenesis of some tumors, but the relationship between Vav2 gene and gastric cancer remains unclear. Purpose of this study is to detect the expression of Vav2 protein in gastric cancer tissues and to evaluate the clinical value of Vav2. Furthermore, both effect of Vav2 gene on invasion and metastasis of gastric cancer cells and its mechanism are investigated in vitro. Results showed that positive rate of Vav2 protein was significantly higher in gastric cancer tissues than in adjacent tissues and notably higher in metastatic lymph nodes than in gastric cancer tissues. Results of western blot were consistent with immunohistochemistry. Expression of Vav2 protein in gastric cancer tissues was related to degree of tumor differentiation, lymph node metastasis, and clinical stages. Inhibition of endogenous Vav2 in BGC823 cells led to significantly decreased cell activity, migration, and invasion ability in vitro, and expression of Rac1, MMP-2, and MMP-9 decreased, whereas expression of TIMP-1 increased. We concluded that Vav2 might promote invasion and metastasis of gastric cancer by regulating some invasion and metastasis-related genes.

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MiR-541-3p suppresses gastric cancer via negative regulation of HSF1

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i11.9 ◽

2021 ◽

Vol 20 (11) ◽

pp. 2293-2298

Author(s):

Zihan Zheng ◽

Peng Zhou ◽

Yangyang Xiao ◽

Qian Liu ◽

Tao Wan

Keyword(s):

Gastric Cancer ◽

Cell Lines ◽

Caspase 3 ◽

Target Prediction ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Mrna Levels ◽

Microrna Target ◽

Gastric Cancer Cells

Purpose: To explore the effects of miR-541-3P on the expression of heat shock transcription factor 1 (HSF1) in gastric cancer cells (GC).Methods: The MicroRNA Target Prediction Database was used to predict whether miR-541-3p interacts with HSF1. Interaction was assessed by dual-luciferase reporter assays. Furthermore, miR-541-3p mRNA levels in GC cell lines were determined by qRT-PCR. Human GC cell lines MKN45 and NCI-N87 were transfected with miR-541-3p mimic. Cell apoptosis, proliferation, invasion, and migration were evaluated using flow cytometry, apoptosis assays, Edu assays, CCK-8 assays, and transwell assays, respectively. Caspase-3, Bcl-2, and cleaved caspase-3 expression levels were determined by western blot.Results: Expression of miR-541-3p was significantly down-regulated in GC cells. Functionally, miR-541-3p mimic inhibited GC cell proliferation, migration, and invasion and induced apoptosis in vitro (p <0.01). Mechanistically, miR-541-3p interacted with HSF1 and inhibited its expression. Overexpression of HSF1 counteracted the effects of miR-541-3p mimic in GC cells.Conclusion: These results indicate that miR-541-3p suppresses the development of GC by targeting HSF1 and thus, is a possible strategy for for the management of GC.

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Yiqi Huayu Jiedu Decoction Inhibits the Invasion and Metastasis of Gastric Cancer Cells through TGF-β/Smad Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/1871298 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Ting-Ting Wu ◽

Jun Lu ◽

Pei-Qiu Zheng ◽

Shen-Lin Liu ◽

Jian Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

In Vivo Studies ◽

Migration And Invasion ◽

Invasion And Metastasis ◽

Gastric Cancer Cells ◽

Smad Pathway ◽

Immunohistochemical Assay

Background.Yiqi Huayu Jiedu Decoction (YHJD) can obviously improve the quality of life of those patients with gastric cancer and prolong their survival.Methods. In vitro experiments, we observe YHJD’s effect on the cells’ proliferation by MTT assay. Cell adhesion assay, wound-healing assay, and Transwell invasion assay serve to detect its influence on cells’ adhesion, migration, and invasion, respectively. Inhibitor (10 μM/L of SB431542) and activator (10 ng/mL of TGF-β) of TGF-β/Smad pathway were used to estimate whether YHJD’s impact on the biological behavior of gastric cancer cells was related to TGF-β/Smad pathway. In in vivo studies, YHJD was administered to the nude mice transplanted with gastric cancer to observe its effect on the tumor. Western blotting and immunohistochemical assay were used to test relevant cytokines of TGF-β/Smad pathway and epithelial-mesenchymal transition (EMT) in MGC-803 cells and the tumor bearing nude mice.Results.YHJD inhibited proliferation, adhesion, migration, and invasion of MGC-803 gastric cancer cells in vitro. In in vivo studies, YHJD reduced the volume of the transplanted tumors. It also enhanced the expression of E-cadherin and decreased the levels of N-cadherin, TGF-β, Snail, and Slug in both MGC-803 cells and the transplanted tumor by western blot assay. The immunohistochemical assay revealed that YHJD raised E-cadherin in the tumors of the mice; on the contrary, the expression of N-cadherin, Twist, vimentin, TGF-βR I, p-Smad2, p-Smad3, Snail, and Slug reduced.Conclusion. YHJD can effectively inhibit the invasion and metastasis of gastric cancer cells. The mechanism may be related to TGF-β/Smad pathway.

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Effects of Huaier Polysaccharide SP1 on Gastric Cancer Cell Proliferation, Apoptosis, Migration, and Invasion by Regulating TGF-β/SMAD Signaling Pathway

Advances in Polymer Technology ◽

10.1155/2020/8486039 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Miaoliang Chen ◽

Ying Lu ◽

Ruili Zhang ◽

Tienan Bi ◽

Shenkang Zhou

Keyword(s):

Gastric Cancer ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Signal Pathway ◽

Migration And Invasion ◽

Dependent Manner ◽

Gastric Cancer Cells

Objective. To study the effects of Huaier polysaccharide SP1 on the proliferation, apoptosis, migration, and invasion of gastric cancer cell line MGC-803 and the underlying mechanism. Methods. MGC-803 cells were cultured in vitro and treated with SP1. The effects of SP1 on the proliferation, apoptosis, migration, and invasion of MGC-803 cells were detected by CCK-8 assay, flow cytometry analysis, and Transwell assay, respectively. Western blot and qRT-PCR were used to detect the expression of related genes. Results. Our study showed that Huaier polysaccharide SP1 could inhibit proliferation, migration, invasion, and promote the apoptosis of MGC-803 cells in vitro in a dose-dependent manner. Huaier polysaccharide SP1 could inhibit the activation of TGF-β/SMAD signal pathway by upregulating SMAD7 expression, thereby downregulating the expression of SOX4, ZEB2, MMP9, Snail, and Slug. Conclusion. Huaier polysaccharide SP1 can regulate the proliferation, apoptosis, migration, and invasion of gastric cancer cells by promoting the expression of SMAD7 and inhibiting the activation of TGF-β/SMAD signal pathway as well as the expression of the downstream oncogenes.

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Overexpression of TC2N is associated with poor prognosis in gastric cancer

10.21203/rs.3.rs-39545/v1 ◽

2020 ◽

Author(s):

Jianbo Xu ◽

Xinde Ou ◽

Jin Li ◽

Qinbo Cai ◽

Kaiyu Sun ◽

...

Keyword(s):

Gastric Cancer ◽

Protein Expression ◽

Cancer Cells ◽

Poor Prognosis ◽

The Cancer Genome Atlas ◽

Gastric Epithelium ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Term Survival

Abstract Background Tac2-N (TC2N) is a tandem C2 domain-containing protein, acting as a novel oncogene or suppressor in different kinds of cancers. However, the status of TC2N expression and its significance in gastric cancer (GC) is still unclear. The present study is aimed to elucidate the clinicopathological significance and prognostic value of TC2N level in GC. Methods We used sequencing data from the Cancer Genome Atlas (TCGA) database to analyze TC2N expression in GC by UALCAN database and Gene Expression Profiling Interactive Analysis tools (GEPIA). TC2N expression level in 12 pairs of fresh GC tissues and adjacent nontumorous tissues was detected by quantitative real-time reverse-transcription polymerase chain reaction(RT-PCR)and Western blot(WB) assays. Immunohistochemical (IHC) staining was used to detect TC2N protein expression in Paraffin-embedded tissues in our center. In vitro proliferation, migration and invasion assays were used to evaluate the effect of TC2N on functional capability of gastric cancer cells. LinkedOmics was used to identify gene expressions associated with TC2N. Results The mRNA and protein expression of TC2N in gastric cancer were both significantly higher than normal gastric mucosa. It was also elevated in gastric cancer cells compared with normal gastric epithelium cell. In vitro assays suggested that TC2N facilitated proliferation, migration and invasion of gastric cancer cells. Bioinformatic analysis showed a widespread impact of TC2N on the transcriptome and a strong interaction with tumor associated genes. We also found that TC2N was an independent prognostic factor for long-term survival in GC patients and its high expression was significantly associated with poor overall survival and recurrence-free survival. Conclusions Our results show that high level of TC2N correlates with poor prognosis in patients with gastric cancer and promotes the development of gastric cancer. Thus, TC2N expression can serve as a prognostic biomarker for patients with gastric cancer.

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Transcription Factor CTCFL Promotes Cell Proliferation, Migration, and Invasion in Gastric Cancer via Activating DPPA2

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/9097931 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Haibo Yao ◽

Qinshu Shao ◽

Yanfei Shao

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Transcription Factor ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Positive Role ◽

Qrt Pcr ◽

The Relationship

Objective. To explore the relationship between CTCFL and DPPA2 and validate the positive role of CTCFL/DPPA2 in cell malignant behaviors in gastric cancer. Methods. We predicted gastric cancer-related transcription factors and corresponding target mRNAs through bioinformatics. Levels of CTCFL and DPPA2 were assessed via qRT-PCR and western blot. In vitro experiments were utilized to assay the cell biological behaviors. CHIP was utilized for the assessment of the targeted relationship between CTCFL and DPPA2. Results. CTCFL and DPPA2 were both highly expressed in gastric cancer cells, and high CTCFLL and DPPA2 could promote cell malignant behaviors. CHIP validated that DPPA2 was a target of CTCFL. In addition, high DPPA2 rescued the repressive impact of CTCFL silencing on the cell proliferation, migration, and invasion in gastric cancer. Conclusion. The transcription factor CTCFL fosters cell proliferative, migratory, and invasive properties via activating DPPA2 in gastric cancer.

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Transcription Factor CTCFL Promotes cell Proliferation, Migration and Invasion in Gastric Cancer Via Activating DPPA2

10.21203/rs.3.rs-46794/v1 ◽

2020 ◽

Author(s):

Haibo Yao ◽

Qinshu Shao ◽

Yanfei Shao

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Transcription Factor ◽

Inhibitory Effect ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Positive Role ◽

Promote Cell Proliferation ◽

Transwell Invasion Assay

Abstract Background: The purpose of this study was to explore the relationship between CTCFL and DPPA2, and validate the positive role of CTCFL/DPPA2 in cell proliferation, migration and invasion in gastric cancer.Methods: Bioinformatics methods were applied for the prediction of gastric cancer-related transcription factors and corresponding target mRNAs. qRT-PCR and western blot were performed to test the levels of CTCFL and DPPA2. Then a series of in vitro experiments were conducted to assay the cell biological behaviors, including CCK-8, colony formation assay, wound healing assay and Transwell invasion assay. CHIP was carried out for assessment of the targeted relationship between CTCFL and DPPA2.Results: CTCFL and DPPA2 were both highly expressed in gastric cancer cells, and high CTCFLL and DPPA2 could promote cell proliferation, migration and invasion. CHIP validated that DPPA2 was a target of CTCFL. In addition, high DPPA2 could reverse the inhibitory effect of CTCFL silencing on the cell proliferation, migration and invasion in gastric cancer.Conclusion: The transcription factor CTCFL promotes cell proliferation, migration and invasion in gastric cancer via activating DPPA2.

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