scholarly journals Bupivacaine suppresses the progression of gastric cancer through regulating circ_0000376/miR-145-5p axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Changqiao Ju ◽  
Jia Zhou ◽  
Hui Miao ◽  
Xin Chen ◽  
Qingyu Zhang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Glucose Transporter ◽  
Lactic Dehydrogenase ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Western Blot Assay

Abstract Background Local anesthetic Bupivacaine commonly used in gastric cancer resection operation has been reported to suppress the progression of gastric cancer. However, the specific mechanism by which Bupivacaine functions is largely unexplored. Methods The viability and metastasis of gastric cancer cells were assessed by Cell counting kit-8 (CCK8) assay and transwell migration and invasion assays. The apoptosis was evaluated by caspase-3 activity detection assay and flow cytometry. The glycolysis was analyzed through detecting the extracellular acidification rate (ECAR) via Seahorse XF 96 Extracellular Flux Analyzer and the expression of glucose transporter type 1 (GLUT1) and lactic dehydrogenase A (LDHA) via Western blot assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circular RNA 0000376 (circ_0000376) and microRNA-145-5p (miR-145-5p). The interaction between circ_0000376 and miR-145-5p was predicted using Circular RNA Interactome database and validated by dual-luciferase reporter assay. Results Bupivacaine restrained the viability, metastasis and glycolytic process while promoted the apoptosis of gastric cancer cells. Bupivacaine decreased the level of circ_0000376 while enhanced the abundance of miR-145-5p in gastric cancer cells. Circ_0000376 accelerated the malignant behaviors of gastric cancer cells. MiR-145-5p directly interacted with circ_0000376 in gastric cancer cells, and miR-145-5p was negatively regulated by circ_0000376. The addition of circ_0000376 or the interference of miR-145-5p partly reversed Bupivacaine-mediated influences in gastric cancer cells. Conclusion Bupivacaine exerted an anti-tumor role to suppress the progression of gastric cancer through reducing the abundance of circ_0000376 and up-regulating miR-145-5p.

scholarly journals Zinc Finger Protein 521, Negatively Regulated by MicroRNA-204-5p, Promotes Proliferation, Motility and Invasion of Gastric Cancer Cells

2019 ◽  
Vol 18 ◽  
pp. 153303381987478 ◽  
Author(s):  
Chen Huan ◽  
Cai Xiaoxu ◽  
Ren Xifang
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Finger Protein

Objective: This study aims to investigate the expression, role, and detailed mechanism of microRNA-204-5p and zinc finger protein 521 in gastric cancer. Methods: Immunohistochemistry was adopted to detect the expressions of zinc finger protein 521 in 82 cases of gastric cancer tissues. Western blot was used to detect the expressions of zinc finger protein 521 in gastric cancer cells and adjacent cells. Moreover, the correlation between zinc finger protein 521 and the prognosis of patients were also evaluated. Cell Counting Kit 8 assay and colony formation assay were performed to figure out the impact of zinc finger protein 521 on the proliferation of gastric cancer cells. By conducting flow cytometry, the effect of zinc finger protein 521 on the apoptosis of gastric cancer cells was determined. The scratch wound healing assay and transwell invasion assay were carried out to determine the effect of zinc finger protein 521 on regulating the motility and invasion of gastric cancer cells. Ultimately, the targeting relationship and interaction between microRNA-204-5p and zinc finger protein 521 were verified by real-time polymerase chain reaction, Western blot, and dual luciferase reporter gene assay. Results: Compared with adjacent cells, zinc finger protein 521 was highly expressed in gastric cancer cells, which was related to TNM stage ( P = .0388), tumor size ( P = .0168), and local lymph node metastasis ( P = .0024). Overexpressed zinc finger protein 521 can promote the proliferation, migration, and invasion of gastric cancer cells and inhibit the apoptosis. Zinc finger protein 521 is a target gene of microRNA-106-5p, and there was a negative correlation between the expression of zinc finger protein 521 and microRNA-204-5p. Conclusion: Zinc finger protein 521 can arrest the apoptosis and enhance the proliferation, migration, and invasion of gastric cancer cells via regulating microRNA-204-5p. Our study may provide novel clues for the treatment of patients with gastric cancer.

scholarly journals CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ling Gao ◽  
Tingting Xia ◽  
Mingde Qin ◽  
Xiaofeng Xue ◽  
Linhua Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
High Morbidity ◽  
Gastric Cancer Cells ◽  
Mirna Sponges ◽  
Gastric Cancer Cell Proliferation

BackgroundGastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown.MethodsCircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK).ResultsThe level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer.ConclusionCollectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer.

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

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.

scholarly journals MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway

2017 ◽  
Vol 25 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Chunsheng Li ◽  
Jingrong Dong ◽  
Zhenqi Han ◽  
Kai Zhang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3′-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.

scholarly journals circCOL1A1 Promotes the Progression of Gastric Cancer Cells through Sponging miR-145 to Enhance RABL3 Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Yue Ma ◽  
Yanyi Ren ◽  
Huitao Wen ◽  
Chengcheng Cui
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
Microrna Sponge ◽  
And Function

Circular RNA has been reported to be a new noncoding RNA which plays important roles in tumor progression. One of the most common functions of circular RNA is to regulate microRNA expression by acting as a microRNA sponge. However, the circular RNA expression profile and function remain mostly unclear in gastric cancer. In the study, we explored the expression and function of circCOL1A1 (hsa_circ_0044556) in gastric cancer. We performed RT-PCR with divergent primers, mRNA stability assay, and RNase R digestion assay to characterize circCOL1A1 in gastric cancer cell lines. qRT-PCR was applied to detect the level of circCOL1A1 in both gastric cancer cell lines and tissues. Gain- and loss-of-function studies were carried out to detect the influence of circCOL1A1 on gastric cancer cells by performing CCK8, migration, and invasion assays. The regulation of the downstream genes was identified by qRT-PCR, western blot assay, dual luciferase assay, and RNA pull-down assay. The results showed that circCOL1A1 was highly expressed in both gastric cancer cells and tissues. Silence of circCOL1A1 inhibited the proliferation, migration, and invasion of gastric cancer cells. circCOL1A1 regulated the expression of miR-145 by acting as a microRNA sponge, and the influence of circCOL1A1 could be abrogated by miR-145 mimics. Our research shows that miR-145 plays its functions through targeting and regulating RABL3. Inhibition of circCOL1A1/miR-145/RABL3 could effectively suppress gastric cancer cell proliferation, migration, and invasion. circCOL1A1 also promote the transformation of M1 into M2 macrophage. Our study identified circCOL1A1 as a novel oncogenic circRNA and will provide more information for gastric cancer therapy.

scholarly journals CircARVCF Contributes to Cisplatin Resistance in Gastric Cancer by Altering miR-1205 and FGFR1

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruirui Zhang ◽  
Huanyu Zhao ◽  
Hongmei Yuan ◽  
Jian Wu ◽  
Haiyan Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Colony Formation ◽  
Xenograft Model ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Western Blot Assay ◽  
Major Barrier

Background: Chemoresistance is a major barrier to the treatment of human cancers. Circular RNAs (circRNAs) are implicated in drug resistance in cancers, including gastric cancer (GC). In this study, we aimed to explore the functions of circRNA Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome (circARVCF) in cisplatin (DDP) resistance in GC.Methods: The expression of circARVCF, microRNA-1205 (miR-1205) and fibroblast growth factor receptor 1 (FGFR1) was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blot assay or immunohistochemistry (IHC) assay. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were performed to evaluate DDP resistance and cell colony formation ability. Transwell assay was conducted to assess cell migration and invasion. Flow cytometry analysis was done to analyze cell apoptosis. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were manipulated to analyze the relationships of circARVCF, miR-1205 and FGFR1. Murine xenograft model was constructed to explore DDP resistance in vivo.Results: CircARVCF level was increased in DDP-resistant GC tissues and cells. CircARVCF silencing inhibited DDP resistance, colony formation and metastasis and induced apoptosis in DDP-resistant GC cells. CircARVCF directly interacted with miR-1205 and miR-1205 inhibition reversed circARVCF silencing-mediated effect on DDP resistance in DDP-resistant GC cells. FGFR1 served as the target gene of miR-1205. MiR-1205 overexpression restrained the resistance of DDP-resistant GC cells to DDP, but FGFR1 elevation abated the effect. In addition, circARVCF knockdown repressed DDP resistance in vivo.Conclusion: CircARVCF enhanced DDP resistance in GC by elevating FGFR1 through sponging miR-1205.

scholarly journals MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yixun Lu ◽  
Benlong Zhang ◽  
Baohua Wang ◽  
Di Wu ◽  
Chuang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cancer Tissues ◽  
Gastric Cancer Progression

Abstract Background Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC. Methods Paired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo. Results GLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo. Conclusions MiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression.

scholarly journals Circular RNA circ-PVT1 contributes to paclitaxel resistance of gastric cancer cells through the regulation of ZEB1 expression by sponging miR-124-3p

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Yan-yan Liu ◽  
Li-ying Zhang ◽  
Wen-zhen Du
Keyword(s):  
Gastric Cancer ◽  
Tumor Model ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Western Blot Assay ◽  
Protein Levels ◽  
Zeb1 Expression ◽  
Resistant Cells

Abstract Gastric cancer (GC) is the fifth most commonly diagnosed malignancy. Paclitaxel (PTX) is an effective first-line chemotherapy drug in GC treatment, but the resistance of PTX attenuates the therapeutic effect. Circular RNA circ-PVT1 can exert the oncogenic effect in GC. But the function of circ-PVT1 involved in PTX resistance of GC is still unknown. In the present study, the expression levels of circ-PVT1, miR-124-3p and ZEB1 in PTX-resistant GC tissues and cells were detected by quantitative real-time polymerase chain reaction (RT-qPCR). PTX resistance in PTX-resistant cells was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The protein levels of Zinc finger E-box binding homeobox 1 (ZEB1), P-glycoprotein (P-gp) and glutathione S-transferase (GST-π) were detected by Western blot assay. Cell apoptosis and invasion were measured in PTX-resistant cells by flow cytometry and transwell invasion assays, severally. The interaction between miR-124-3p and circ-PVT1 or ZEB1 was predicted by starBase software, and then verified by the dual-luciferase reporter assay. The role of circ-PVT1 in PTX resistance of GC in vivo was measured by xenograft tumor model. Our results showed that circ-PVT1 expression was up-regulated in PTX-resistant GC tissues and cells. Circ-PVT1 down-regulation enhanced PTX sensitivity in PTX-resistant GC cells by negatively regulating miR-124-3p. ZEB1 served as a direct target of miR-124-3p. Circ-PVT1 enhanced ZEB1 expression by sponging miR-124-3p. Circ-PVT1 knockdown increased PTX sensitivity of GC in vivo. Taken together, our studies disclosed that circ-PVT1 facilitated PTX resistance by up-regulating ZEB1 mediated via miR-124-3p, suggesting an underlying therapeutic strategy for GC.

Circular RNA circ_0000039 enhances gastric cancer progression through miR-1292-5p/DEK axis

2020 ◽  
pp. 1-11
Author(s):  
Dengguo Fan ◽  
Changjiang Wang ◽  
Deyuan Wang ◽  
Ning Zhang ◽  
Tao Yi
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Human Cancer ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Poor Differentiation

BACKGROUND: Circular RNA (circRNA) is a class of non-coding RNA that is vital for regulating gene expression and biological functions. Mounting studies demonstrate that circRNA is crucial for human cancer development. However, the role of circ_0000039 in gastric cancer (GC) remains uncertain. METHODS: Normal human gastric tissues and GC tissue samples were collected, and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression levels of circ_0000039, miR-1292-5p, and DEK. GC cell lines with overexpression and low expression of circ_0000039 were constructed. Cell counting kit-8 (CCK-8), scratch healing and Transwell experiments were used to assess the function of circ_0000039 on the proliferation, migration and invasion of GC cells. Bioinformatics analysis and dual-luciferase reporter assays were employed to detect the targeting relationship between circ_0000039 and miR-1292-5p. RESULTS: Circ_0000039 expression was up-regulated in GC tissues and cell lines, and it was significantly related with poor differentiation of tumor tissues. In addition, circ_0000039 overexpression enhanced the proliferation, migration and invasion of GC cells, while circ_0000039 depletion inhibited these malignant biological behaviors. In terms of mechanism, it was found that circ_0000039 promoted the proliferation and progression of GC cells by adsorbing miR-1292-5p and up-regulating the expression of DEK. CONCLUSION: Circ_0000039 is a new oncogenic circRNA in GC, which regulates the miR-1292-5p/DEK axis to modulate the malignant biological behaviors of GC.

Sign in / Sign up

Export Citation Format

Share Document