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 GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hong Chen ◽  
Lu Xu ◽  
Zhi-li Shan ◽  
Shu Chen ◽  
Hao Hu
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Western Blot ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

Abstract Background Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported. Methods Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot. Results The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes. Conclusions These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.

scholarly journals Potent and specific MTH1 inhibitors targeting gastric cancer

2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Wenjuan Zhou ◽  
Liying Ma ◽  
Jing Yang ◽  
Hui Qiao ◽  
Lingyu Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Malignant Tumors ◽  
Inhibitory Effect ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Dntp Pool ◽  
Cancer Tissues

Abstract Human mutT homolog 1(MTH1), the oxidized dNTP pool sanitizer enzyme, has been reported to be highly expressed in various malignant tumors. However, the oncogenic role of MTH1 in gastric cancer remains to be determined. In the current study, we found that MTH1 was overexpressed in human gastric cancer tissues and cells. Using an in vitro MTH1 inhibitor screening system, the compounds available in our laboratory were screened and the small molecules containing 5-cyano-6-phenylpyrimidine structure were firstly found to show potently and specifically inhibitory effect on MTH1, especially compound MI-743 with IC50 = 91.44 ± 1.45 nM. Both molecular docking and target engagement experiments proved that MI-743 can directly bind to MTH1. Moreover, MI-743 could not only inhibit cell proliferation in up to 16 cancer cell lines, especially gastric cancer cells HGC-27 and MGC-803, but also significantly induce MTH1-related 8-oxo-dG accumulation and DNA damage. Furthermore, the growth of xenograft tumours derived by injection of MGC-803 cells in nude mice was also significantly inhibited by MI-743 treatment. Importantly, MTH1 knockdown by siRNA in those two gastric cancer cells exhibited the similar findings. Our findings indicate that MTH1 is highly expressed in human gastric cancer tissues and cell lines. Small molecule MI-743 with 5-cyano-6-phenylpyrimidine structure may serve as a novel lead compound targeting the overexpressed MTH1 for gastric cancer treatment.

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 MiR-496 Inhibits the Proliferation Through Targeting LYN and AKT/mTOR Signaling Pathway in Gastric Cancer

2020 ◽  
Author(s):  
Rui Su ◽  
Enhong Zhao ◽  
Jun Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Mtor Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Ags Cells

Abstract MiRNA operates as a tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis and metabolic process. In the present research, we investigated the effect and mechanism of miR496 in human gastric cancer cells. Cell proliferation was measured by CCK8 and clonogenic assay. Transwell test was performed to detect cell migration and invasion. Flow cytometry analysis was used to evaluate cell apoptosis. Bioinformatics software targetscan was used for the screening of miR-496’s target gene. MiR-496 was down regulated in three gastric cancer cell lines, SGC-790, AGS and MKN45 compared with normal gastric epithelial cell line GES-1. MiR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 h and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. In addition, miR-496 mimics induced the apoptosis through up regulating the levels of Bax and Active Caspase3 and down regulating the levels of Bcl-2 and Total Caspase3. Bioinformatics analysis showed that there was a binding site between miR-496 and LYN kinase (LYN). MiR-496 mimics could inhibit the expression of LYN in AGS cells. The overexpression of LYN blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496 in gastric cancer cells. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment of gastric cancer.

scholarly journals miR-182-5p improves the viability, mitosis, migration, and invasion ability of human gastric cancer cells by down-regulating RAB27A

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Yuling Li ◽  
Shudong Chen ◽  
Zhengfei Shan ◽  
Liyan Bi ◽  
Shengqiang Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Migration Ability ◽  
Invasion And Migration ◽  
Gene Assay ◽  
And Migration

We investigated the effect of miR-182-5p on the viability, proliferation, invasion, and migration ability of human gastric cells by regulating the expression of RAB27A. Real-time PCR assay was used to detect the expression of miR-182-5 and RAB27A in human gastric carcinoma tissues, para-carcinoma tissues, and different cell lines. Western blotting was also used to determine the RAB27A expression in both tissues and cell lines. We chose the HGC-27 cell line as experiment subject as it demonstrated the highest miR-182-5p level. HGC-27 cells were transfected with different vectors and the cell viability, mitosis, invasion, and migration ability were measured through MTT assay, flow cytometry (FCM) analysis, Transwell assay, and wound healing assay. In comparison with the normal tissues, miR-182-5p is expressed at a higher level in gastric cancer (GC) tissues, while RAB27A is expressed at a lower level in cancerous tissues. The down-regulation of miR-182-5p and up-regulation of RAB27A can significantly decrease the viability, migration, invasion, and mitosis of HGC-27 cells. The target relationship between miR-182-5p and RAb27A was confirmed through a dual-luciferase reporter gene assay and Western blot assay. miR-182-5p enhances the viability, mitosis, migration, and invasion of human GC cells by down-regulating RAB27A.

scholarly journals METTL3 promotes the proliferation and mobility of gastric cancer cells

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Sen Lin ◽  
Jianing Liu ◽  
Wen Jiang ◽  
Peng Wang ◽  
Chao Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Apoptotic Pathway ◽  
Mechanistic Investigation

AbstractMethyltransferase-like 3 (METTL3) was originally known to be responsible for N6-methyladenosine (m6A) modification of mRNA. Recent studies have found that METTL3 plays important roles in a variety of tumors by regulating the translation of oncogenes. However, the functional and regulating mechanisms of METTL3 in human gastric cancer have not yet been understood. Here we knocked down METTL3 in human gastric cancer cell lines, AGS and MKN45, by using shRNA transfection. RT-qPCR assay and western blotting verified the effectiveness of RNA interference on mRNA and protein levels, respectively. Then we found that METTL3 knockdown inhibited cell proliferation, migration and invasion in AGS and MKN45 cells. Moreover, METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. Mechanistic investigation suggested that METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1. In conclusion, our study reveals that down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 may be a potential target for the treatment of human gastric cancer.

LINC01207 is up-regulated in gastric cancer tissues and promotes disease progression by regulating miR-671-5p/DDX5 axis

2021 ◽  
Author(s):  
Hongquan Liu ◽  
Xiaoyu Liu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Bioinformatics Analysis ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Downstream Target ◽  
Proliferation And Metastasis ◽  
Cancer Tissues

Abstract LINC01207 is involved in the progression of some cancers. This study was designed to delve into the biological function and mechanism of LINC01207 in gastric cancer. qPCR was adopted to examine the expression levels of LINC01207, miR-671-5p, DDX5 mRNA in gastric cancer tissues and cells. After LINC01207 was overexpressed or depleted, MTT and BrdU assays were conducted to detect cell proliferation. Transwell assay was employed to detect cell migration and invasion. Western blot was used to detect the expression of DDX5 protein in cells. Bioinformatics analysis, luciferase reporter assay and RNA pull-down assay were performed to predict and validate the binding site between miR-671-5p and LINC01207 or DDX5. LINC01207, DDX5 mRNA were up-regulated in gastric cancer, while miR-671-5p was down-regulated; high expression of LINC01207 and transfection of miR-671-5p inhibitors facilitated the proliferation of gastric cancer cells; however, knocking down LINC01207 and the overexpression of miR-671-5p mimics had opposite biological effects. LINC01207 and miR-671-5p were interacted and miR-671-5p was negatively regulated by LINC01207. MiR-671-5p could reverse the function of LINC01207. DDX5 was a downstream target of miR-671-5p and was positively modulated by LINC01207. LINC01207 promotes the proliferation and metastasis of gastric cancer cells by regulating miR-671-5p/DDX5 axis.

NSD1 stimulated survival and migration of gastric cancer cells through WNT10B

2021 ◽  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Expression Levels ◽  
Gastric Cancer Cell Lines ◽  
And Migration ◽  
Cancer Tissues

Background and objective: To assess the expression of Nuclear receptor binding SET domain protein 1 (NSD1) in human gastric cancer tissues and cells and investigate its possible role in gastric cancer. Methods: TCGA database was used to assess the expression levels of NSD1 in human gastric cancer tissues. Immunoblot assays were performed to detect NSD1 expression levels in gastric cancer cell lines. MTT and colony formation assays were conduced to detect its role in the survival of gastric cancer cells. Wound closure and transwell were performed to investigate the effects of NSD1 on the motility of gastric cancer cells. Immunoblot assays were also conducted to confirm its effects on WNT10B/β-catenin pathway. Results: We found the high expression levels of NSD1 in human gastric cancer tissues and cell lines. NSD1 depletion suppressed the survival and motility of gastric cancer cells. Additionally, we revealed NSD1 activated the WNT10B/β-catenin pathway, therefore promoted gastric cancer progression. Conclusion: We revealed the high NSD1 expression in gastric cancer tissues and cells, and thought NSD1 could serve as a promising gastric cancer target.

scholarly journals LncRNA SNHG7 Regulates Gastric Cancer Progression by miR-485-5p

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhongsong Zhao ◽  
Xueping Liu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter Assay ◽  
Gastric Cancer Cells ◽  
Cancer Tissues ◽  
Gastric Cancer Progression ◽  
Dual Luciferase Reporter Assay

Background. Long noncoding ribonucleic acids (lncRNAs) were closely related to the development of gastric cancer. This study investigated the effect of SNHG7 on gastric cancer progression and its potential molecular mechanism. Methods. SNHG7 and microRNA-485-5p (miR-485-5p) expressions in gastric cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), wound healing, and transwell experiments were used to detect cell proliferation, migration, and invasion. The dual luciferase reporter assay, RNA immunoprecipitation (RIP) experiment, and Pearson’s correlation analysis were used to confirm the relationship between SNHG7 and miR-485-5p. Results. SNHG7 expression was increased in human gastric cancer tissues and cells. Knockdown of SNHG7 could notably inhibit the gastric cancer cells proliferation, migration, and invasion. The dual-luciferase reporter assay and RIP experiments proved that miR-485-5p was a direct target of SNHG7. At the same time, further experiments demonstrated that miR-485-5p inhibition reversed the suppression of SNHG7 knockdown on gastric cancer cells proliferation, migration, and invasion. Conclusions. SNHG7 knockdown could hamper gastric cancer progression via inhibiting miR-485-5p expression, providing a novel understanding for gastric cancer development.

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