scholarly journals Distinct functions and prognostic values of RORs in gastric cancer

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 424-434
Author(s):  
Feng Gu ◽  
Yuming Liu ◽  
Yuan Liu ◽  
Shujie Cheng ◽  
Jihong Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Retinoic Acid Receptor ◽  
Wnt Signaling Pathway ◽  
Her2 Status ◽  
Orphan Receptors ◽  
Kaplan Meier ◽  
And Migration ◽  
Kaplan Meier Plotter ◽  
Proliferation And Migration

AbstractRetinoic acid receptor-related orphan receptors (RORs) are frequently abnormally expressed in several human malignancies, including gastric cancer (GC). RORs are involved in the development and progression of GC through Wnt signaling pathway receptors and other common receptors. However, the prognostic roles of individual RORs in patients with GC remain elusive. We accessed the prognostic roles of three RORs (RORα, RORβ, and RORγ) through “The Kaplan–Meier plotter” (KM plotter) database in patients with GC. For all patients with GC who were followed for 20 years, the low mRNA expression of all three RORs showed a significant correlation with better outcomes. We further accessed the prognostic value of individual RORs in different clinical pathological features including Lauren classification, clinical stages, pathological grades, HER2 status, and different treatments methods. The RORs demonstrated critical prognostic roles in GC. Expressions of RORs were higher in GC tissues when compared with normal gastric tissues. Moreover, knockdown of RORs significantly inhibited cell proliferation and migration, suggesting an oncogenic role of RORs in human GC. These findings suggest potential roles of RORs as biomarkers for GC prognosis and as oncogenes in GC.

scholarly journals LncRNA HCG11 promotes proliferation and migration in gastric cancer via targeting miR-1276/CTNNB1 and activating Wnt signaling pathway

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hua Zhang ◽  
Haitao Huang ◽  
Xiaomei Xu ◽  
Haiying Wang ◽  
Jianxiang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Function Analysis ◽  
Wnt Signaling Pathway ◽  
Tumor Formation ◽  
Tumor Promoter ◽  
Luciferase Reporter ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Gastric cancer (GC) is one common cancer which occurs in the stomach leading to high mortality around the world. Long non-coding RNAs (lncRNAs) were found overexpressed or silenced in the occurrence and progression of multiple cancers including GC. Method The gene expression level in GC tissues and cells were analyzed by RT-qPCR. CCK-8, colony formation, flow cytometry and transwell assays were performed for the function analysis of HLA complex group 11 (HCG11). The mechanism study for HCG11 was conducted using RIP, RNA pull down and luciferase reporter assays. Results HCG11 was discovered highly expressed in GC tissues and cells. Depletion experiments were used to evaluate HCG11 silence on cell proliferation, migration and apoptosis. Moreover, Wnt signaling pathway was found as a tumor promoter in GC. RIP assay, RNA pull down assay and luciferase reporter assay were performed to illustrate the relationship of HCG11, miR-1276 and CTNNB1. Rescue assays revealed that HCG11/miR-1276/CTNNB1 axis regulated the incidence and development of GC. Tumor formation in mice proved that HCG11 was negatively correlated with miR-1276 and had positively correlation with CTNNB1. Conclusion Overall, HCG11 accelerated proliferation and migration in GC through miR-1276/CTNNB1 and Wnt signaling pathway, revealing that HCG11 could be a brand new target for GC.

scholarly journals Prognostic values of signal transducers activators of transcription in gastric cancer

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Yujie Zhang ◽  
Chaoran Yu
Keyword(s):  
Gastric Cancer ◽  
Cd8 T Cells ◽  
Prognostic Markers ◽  
Risk Group ◽  
Her2 Status ◽  
Signal Transducers ◽  
Kaplan Meier ◽  
Infiltrating Cells ◽  
Kaplan Meier Plotter

AbstractThe signal transducers and activators of transcription genes family (STATs) have been well studied as prognostic predictors for various solid tumors, but their prognostic values in gastric cancer (GC) patients have not been fully elucidated. The ‘Kaplan–Meier plotter’ and multiple public available databases were used for the characterization of the prognostic roles of STATs family in GC. The results indicated that high mRNA expression of all individual STATs, except STAT3 and STAT6, were significantly associated with favorable overall survival (OS) in GC. Moreover, the prognostic values of STATs were further characterized in subtypes, including HER2 status, Lauren’s classification, differentiation, and clinical stages. Moreover, the prognostic value of STATs signature was also characterized. Low risk group displayed a significantly favorable OS than high risk (HR: 1.71; 95% CI: 1.09–2.66, P=0.0184). In addition, STATs showed distinct expression between GC and normal groups. Meanwhile, comparable high correlation between STATs and tumor immune infiltrating cells (TIICs) was also observed. STAT4 displayed highest correlation with dendritic cells (correlation = 0.716, P=1.63e-59) and CD8+ T cells (correlation = 0.697, P=5.02e-55). In conclusion, our results suggest that all individual STATs, except STAT3 and STAT6, may act as prognostic markers in GC.

scholarly journals Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yan Zhang ◽  
Lin Chen ◽  
Xuanting Ye ◽  
Zhixiong Wu ◽  
Zeyu Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Parameter Analysis ◽  
Cell Proliferation And Migration ◽  
Potential Biomarker ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Forkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. Exosome was suggested to mediate cell communication by delivering active molecules in cancers. However, the existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (GC) were not clear. This study aims to investigate the potential role of FOXM1 related long noncoding RNA (FRLnc1) in exosomes in GC. Results The prepared CD63 immunomagnetic beads (CD63-IMB) had the characteristics of good dispersity and high magnetic response. The isolated exosomes were presented with elliptical membranous particles under a transmission electron microscope (TEM), with the particle size of 89.78 ± 4.8 nm. Western blot (WB) results showed that the exosomes were rich in CD9 and CD81. The Dil-labeled exosomes were distributed around cytoplasm and nucleus of cells by imaging flow cytometry (IFC) analysis. The results of quantitative real-time PCR (qRT-PCR) revealed that the FRLnc1 expressions were up-regulated in GC cells, tumor tissues, and serum of GC patients. An obviously up-regulated FRLnc1 expression was found in serum exosomes of GC patients. Up-regulation of FRLnc1 expression was closely correlated to lymph node metastasis (LNM) and TNM stage with the combination of relevant clinicopathological parameter analysis. The in vitro functional analyses demonstrated that FRLnc1 knockdown by RNA interference suppressed cell proliferation and migration in HGC-27 cells, whereas FRLnc1 overexpression promoted cell proliferation and migration in MKN45 cells. After exosome treatment, the FRLnc1 expression was significantly increased in MKN45 cells, and the MKN45 cells showed increased ability of proliferation and migration. Conclusion GC cells-derived exosomes played roles in promoting the growth and metastasis of GC by transporting FRLnc1, suggesting that FRLnc1 in the exosomes may be a potential biomarker for the diagnosis and treatment of GC. The delivery of FRLnc1 by the exosomes may provide a new way for the treatment of GC. Trial registration 2020-KYSB-094. Registered 23 March 2020—Retrospectively registered Graphic abstract

miR-635 targets KIFC1 to inhibit the progression of gastric cancer

2020 ◽  
Vol 68 (8) ◽  
pp. 1357-1363
Author(s):  
Feng-Yu Cao ◽  
Yong-Bin Zheng ◽  
Chao Yang ◽  
Su-Yang Huang ◽  
Xiao-Bo He ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Gene Assay ◽  
Kaplan Meier Plotter

Accumulating studies have shown that the dysregulation of microRNAs is related to the carcinogenesis and development of gastric cancer (GC), and the role of miR-635 in GC remains largely unknown. miR-635 and Kinesin Family Member C1 (KIFC1) mRNA expression in GC tissues and paracancerous tissues and cells were detected by quantitative real-time PCR. KIFC1 protein expression in GC tissues and paracancerous normal tissues and cells was detected by immunohistochemistry and western blot. Cell proliferation was monitored by Cell Counting Kit-8 assay and 5-bromo-2′-deoxyuridine assay. Transwell assay was employed to detect the migration and invasion of GC cells. The dual-luciferase reporter gene assay was adopted to detect the targeting relationship between miR-635 and KIFC1. Compared with paracancerous tissues, miR-635 expression was remarkably decreased in GC tissues; conversely, KIFC1 expression was significantly increased. Compared with human normal gastric epithelial cell GSE-1, miR-635 expression was markedly decreased in GC cell lines. Meanwhile, KIFC1 expression was significantly increased, and the Kaplan-Meier Plotter database showed that its high expression was remarkably associated with poor prognosis. Additionally, miR-635 can negatively regulate KIFC1. miR-635 can target KIFC1 to inhibit proliferation, migration and invasion of GC cells. Collectively, miR-635 is lowly expressed in GC, and it inhibits proliferation, migration and invasion of GC cells via regulating KIFC1.

scholarly journals MicroRNA-200b reduced ZEB1 to inhibit cell proliferation and migration in human gastric cancer

2020 ◽  
Author(s):  
He Chen ◽  
Pengcheng Liu ◽  
Lei Wang ◽  
Yanxia Yu ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Cyclin D1 ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
And Migration ◽  
Tgf Β1 ◽  
Proliferation And Migration

Abstract BACKGROUND: Gastric cancer (GC) is one of the most common malignant cancers, with high morbidity and mortality rates worldwide. The present study was to explore whether miR-200b is a tumor suppressor in GC and to unveil the potential mechanisms. METHODS: Levels of c-Myc, Cyclin D1, MMP-3 and MMP-9 expression were detected respectively by qRT-PCR and Western blot assay. BrdU proliferation assay, Cell cycle analysis, Wound-healing and Transwell assays were used to study the role of miR-200b with inhibitor, mimics or ZEB1-RNAi in TGF-β1-treated SGC-7901/DDP cells. The xenograft model with nude mice was established to unveil the role of miR-200b in vivo.RESULTS: Compared with the paracancerous tissues, miR-200b was decreased in GC patients and SGC-7901/DDP cells. Lower level of miR-200b induced by its inhibitor promoted TGF-β1-treated SGC-7901/DDP cells proliferation and migration, and increased the levels of c-Myc, Cyclin D1, MMP-3, MMP-9, β-catenin and APC. Interestingly, miR-200b mimics and ZEB1-RNAi were able to reduce the proliferation and migration of TGF-β1-induced SGC-7901/DDP cells as well as their levels of c-Myc, Cyclin D1, MMP-3 MMP-9, β-catenin and APC. In addition, ZEB1 was indeed the potential target of miR-200b identified by dual luciferase reporter gene assay. Xenograft model also suggested that over-expression of miR-200b suppressed the growth of tumor in vivo. CONCLUSION: Taken together, our findings suggest that miR-200b be likely to play an important role in activating TGF-β1-induced SGC-7901/DDP cells and perform as a tumor suppressor by targeting ZEB1 in GC. What’s more, miR-200b may modulate Wnt/β-catenin signaling pathway in TGF-β1-induced SGC-7901/DDP cells.

scholarly journals CLIC1 facilitates cancer associated fibroblast activation and gastric cancer progression via integrins/NF-κB pathway

2020 ◽  
Author(s):  
Min Meng ◽  
Hong-Bo Wang ◽  
Su-Zhen Song ◽  
Rong Sun ◽  
Yu Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Neutralizing Antibodies ◽  
Molecular Mechanisms ◽  
Stem Cell Markers ◽  
Cancer Stem Cell Markers ◽  
Cancer Associated Fibroblast ◽  
And Migration ◽  
Proliferation And Migration

Background: Gastric cancer (GC) is one of the most common and lethal cancers and the prognosis of GC patients remains very poor. Cancer-associated fibroblasts (CAFs) largely facilitate the progression of GC but the underlying molecular mechanisms remain elusive despite numerous studies. Here, we investigated the role of CLIC1 in CAF activation and GC. Methods: qRT-PCR and western blot were performed to determine expression levels of cytokines, transcription factors and related proteins such as CAF markers. MTT assay was used to examine the proliferation of GC cells while transwell assay and tumorsphere formation assay were done to measure the migration, invasion and stemness of GC cells. Conditioned medium model was used to examine the intercellular communication between CAFs and GC cells. Results: Overexpression of CLIC1 in fibroblasts induced CAF activation and enhanced cell proliferation and migration. Also, CLIC1 up-regulated integrins/NF-κB signaling in CAFs. CLIC1-overexpressed fibroblasts promoted proliferation and migration of GC cells and up-regulated cancer stem cell markers and promoted EMT program of GC cells. IL-6 and IL-8 neutralizing antibodies inhibit the pro-tumor effects of CLIC1-overexpressing fibroblasts on GC cells. Further, knockdown CLIC1 in GC cells suppressed activation of CAF. Conclusions: CLIC1 overexpression activates CAF via up-regulating integrins/NF-κB signaling and activated CAF releases IL-6 and IL-8 to promote multiple malignant phenotypes of GC cells. These results implicate an essential role of CLIC1 in CAF activation and GC progression, which suggests that CLIC1 could serve as a potential target for GC therapy.

scholarly journals DOK5 as a Prognostic Biomarker of Gastric Cancer Immunoinvasion: A Bioinformatics Analysis

2022 ◽  
Vol 2022 ◽  
pp. 1-22
Author(s):  
Fengyong Luo ◽  
Zhihuai Wang ◽  
Shuai Chen ◽  
Zhenbo Luo ◽  
Gaochao Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Data ◽  
Bioinformatics Analysis ◽  
Kaplan Meier ◽  
Pathogenic Genes ◽  
Protein Group ◽  
High Level ◽  
Docking Protein ◽  
Kaplan Meier Plotter

Background. Docking protein 5 (DOK5) is a member of the docking protein group of membrane proteins and is an adapter protein involved in signal transduction. Nevertheless, the role of DOK5 expression in the prognosis of gastric cancer (GC) remains unclear. Methods. In this study, clinical prognostic parameters and survival data related to DOK5, in patients with GC, were analyzed using bioinformatics analysis comprising Oncomine and TIMER, UALCAN database, Kaplan-Meier plotter, GEPIA, GSEA, DAVID, and cBioPortal websites. Results. In our study, GC contained various DOK5 expressions, which forecasted poor survival outcomes. Moreover, our research showed that high DOK5 could predict high-level infiltration of several GC immune cells, as evidenced by M1, TAM, M2, B cell, and T cell failure. Hence, DOK5 might become a new gastric cancer biomarker and therapeutic target. In the following analysis, in order to explore the prognostic value of DOK5 in GC, more clinical trials are needed to validate our results. Conclusions. Through multiple database verifications, DOK5 was found to be part of the pathogenic genes for GC. Thus, it can change the formation and progression of tumors by acting on human immunity.

scholarly journals CSTB Downregulation Promotes Cell Proliferation and Migration and Suppresses Apoptosis in Gastric Cancer SGC-7901 Cell Line

2016 ◽  
Vol 24 (6) ◽  
pp. 487-494 ◽  
Author(s):  
Jian Zhang ◽  
ZhenFeng Shi ◽  
JinXing Huang ◽  
XiaoGuang Zou
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Control Group ◽  
Human Gastric Cancer ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Development Of Gastric Cancer ◽  
Proliferation And Migration

This study aimed to investigate the pivotal role of cystatin B (CSTB) in the development of gastric cancer and to explore its possible regulatory mechanism. Human gastric cancer SGC-7901 cells as a model in vitro were transfected with plasmid PCDNA3.1-CSTB and siRNA-CSTB using Lipofectamine 2000. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to determine the relative expression of CSTB and PI3K/Akt/mTOR pathway-related protein. Moreover, MTT assay, Transwell assay, and flow cytometry were used to assess cell proliferation, migration, and apoptosis, respectively. The results showed that CSTB was significantly downregulated in SGC-7901 cells compared with gastric epithelial cells. CSTB was successfully overexpressed and suppressed after cells were transfected with pc-CSTB and si-CSTB, respectively. Moreover, cell viability and migration were significantly decreased after being transfected with pc-CSTB when compared with the control group, while being obviously increased after transfection with si-CSTB. However, cell apoptosis was significantly induced after being transfected with pc-CSTB, while being obviously suppressed after transfection with si-CSTB. Besides, the expression levels of p-PI3K, p-Akt, and p-mTOR proteins were all significantly decreased in the pc-CSTB transfection group when compared with the control group, while being increased in the si-CSTB transfection group. Our findings suggest that CSTB downregulation may promote the development of gastric cancer by affecting cell proliferation and migration, and the PI3K/Akt/mTOR signaling pathway was activated in this process. CSTB may serve as a potential therapeutic target for gastric cancer.

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