EDD1 predicts prognosis and regulates gastric cancer growth in vitro and in vivo via miR-22

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Min Yang ◽  
Nan Jiang ◽  
Qi-wei Cao ◽  
Qing Sun
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Patient Survival ◽  
Underlying Mechanism ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

Abstract Gastric cancer is the most common digestive malignant tumor worldwild. EDD1 was reported to be frequently amplified in several tumors and played an important role in the tumorigenesis process. However, the biological role and potential mechanism of EDD1 in gastric cancer remains poorly understood. In this study, we are aim to investigate the effect of EDD1 on gastric cancer progression and to explore the underlying mechanism. The results showed the significant up-regulation of EDD1 in -gastric cancer cell tissues and lines. The expression level of EDD1 was also positively associated with advanced clinical stages and predicted poor overall patient survival and poor disease-free patient survival. Besides, EDD1 knockdown markedly inhibited cell viability, colony formation, and suppressed tumor growth. Opposite results were obtained in gastric cancer cells with EDD1 overexpression. EDD1 knockdown was also found to induce gastric cancer cells apoptosis. Further investigation indicated that the oncogenic role of EDD1 in regulating gastric cancer cells growth and apoptosis was related to its PABC domain and directly through targeting miR-22, which was significantly down-regulated in gastric cancer tissues. Totally, our study suggests that EDD1 plays an oncogenic role in gastric cancer and may be a potential therapeutic target for gastric cancer.

scholarly journals The circBVES Acts as a Sponge of miR-145-5p to Promote Gastric Cancer Glycolysis and Progression Through Regulating HMGB3 Expression

2020 ◽  
Author(s):  
Lu Jin ◽  
Zhiwei He ◽  
Changhao Zhu ◽  
Guoliang Xiao ◽  
Xianjin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Gastric Cancer Cells ◽  
Repressive Effect ◽  
Cancer Tissues

Abstract Background: CircRNA is a new type of non-coding RNA that has attracted much attention for involvement in the development and progression of various human diseases, especially cancer. The most reported role of circRNA in many tumors is ‘MiRNA sponge’. We aimed to investigate the role of circBVES in the proliferation and glycolysis of gastric cancer cells and its molecular mechanisms.Methods: In this study, higher CircBVES expression in gastric cancer tissues was detected by RNA sequencing. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of CircBVES in gastric cancer tissues, and the relationship between the expression of CircBVES and prognosis was further analyzed. Then, the effects of CircBVES on the growth and glycolysis of gastric cancer cells were investigated through in vitro and in vivo functional experiments. The interaction between CircBVES and miR-145-5p was detected by bioinformatics analysis, luciferase activity assay and RNA immunoprecipitation.Results: We found that the expression of CircBVES in gastric cancer tissues was evidently up-regulated, and its level was closely correlated with the prognosis of patients with gastric cancer. Inhibition of CircBVES decreased cell proliferation and glycolysis in vitro. Low expression of CircBVES inhibited tumor growth in vivo. Mechanism analysis showed that CircBVES may serve as a competitive endogenous RNA of miR-145-5p to reduce the expression of miR-145-5p in gastric cancer cells, and relieve the repressive effect of miR-145-5p on target genes HMGB3 and cycle-related proteins CCNE1 and CDK2.Conclusions: Our results suggest that CircAGFG1 may promote the progress of gastric cancer through the CircBVES / miR-145-5p / HMGB3 axis, providing a new target for the treatment of gastric cancer cells.

scholarly journals CircCNIH4 inhibits gastric cancer progression via regulating DKK2 and FRZB expression and Wnt/β-catenin pathway

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Qi Shi ◽  
Chuanwen Zhou ◽  
Rui Xie ◽  
Miaomiao Li ◽  
Peng Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Gastric Cancer Cells ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs) have been reported to play an important role in tumor progression in various cancer types, including gastric cancer. The aim of this study was to investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer and the underlying mechanism. Methods The expression levels of circCNIH4 and Wnt antagonist genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of β-catenin, Ki67, Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) were measured by western blot. Ectopic overexpression or knockdown of circCNIH4, proliferation, apoptosis, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assay in vitro, and in vivo experiment, were employed to assess the role of circCNIH4 in gastric cancer. Results CircCNIH4 was downregulated in gastric cancer tissues and cells. Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration and invasion and promoted apoptosis by inactivating Wnt/β-catenin pathway in vitro. CircCNIH4 induced the expression of DKK2 and FRZB in gastric cancer cells. Moreover, silencing of DKK2 or FRZB reversed circCNIH4 overexpression-mediated effects on gastric cancer cells. Additionally, circCNIH4 suppressed tumor growth via regulating DKK2 and FRZB expression in gastric cancer in vivo. Conclusion Our study demonstrated that circCNIH4 played a tumor-inhibiting role through upregulating DKK2 and FRZB expression and suppressing Wnt/β-catenin pathway in gastric cancer, which might provide a potential biomarker for the diagnosis and treatment of gastric cancer.

scholarly journals Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1088 ◽  
Author(s):  
I-Han Wang ◽  
Tzu-Ting Huang ◽  
Ji-Lin Chen ◽  
Li-Wei Chu ◽  
Yueh-Hsin Ping ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Endoplasmic Reticulum ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Nuclear Translocation ◽  
Mevalonate Pathway ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Progression

The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.

scholarly journals miR-125b Suppresses Proliferation and Invasion by Targeting MCL1 in Gastric Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shihua Wu ◽  
Feng Liu ◽  
Liming Xie ◽  
Yaling Peng ◽  
Xiaoyuan Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Clinical Stage ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Progression

Understanding the molecular mechanisms underlying gastric cancer progression contributes to the development of novel targeted therapies. In this study, we found that the expression levels of miR-125b were strongly downregulated in gastric cancer and associated with clinical stage and the presence of lymph node metastases. Additionally, miR-125b could independently predict OS and DFS in gastric cancer. We further found that upregulation of miR-125b inhibited the proliferation and metastasis of gastric cancer cells in vitro and in vivo. miR-125b elicits these responses by directly targeting MCL1 (myeloid cell leukemia 1), which results in a marked reduction in MCL1 expression. Transfection of miR-125b sensitizes gastric cancer cells to 5-FU-induced apoptosis. By understanding the function and molecular mechanisms of miR-125b in gastric cancer, we may learn that miR-125b has the therapeutic potential to suppress gastric cancer progression and increase drug sensitivity to gastric cancer.

scholarly journals LncRNA FEZF1-AS1 Promotes Multi-Drug Resistance of Gastric Cancer Cells via Upregulating ATG5

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhifu Gui ◽  
Zhenguo Zhao ◽  
Qi Sun ◽  
Guoyi Shao ◽  
Jianming Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Multi Drug Resistance ◽  
Gastric Cancer Cells ◽  
Poor Overall Survival

Long non-coding RNAs (lncRNAs) play important roles in human cancers including gastric cancer (GC). Dysregulation of lncRNAs is involved in a variety of pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of FEZF1-AS1 in chemoresistance of GC remain unknown. In this study, we aimed to determine the role of FEZF1-AS1 in chemoresistance of GC. The level of FEZF1-AS1 in GC tissues and GC cell lines was assessed by qRT-PCR. Our results showed that the expression of FEZF1-AS1 was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identified that high level of FEZF1-AS1 is an independent predictor for poor overall survival. Increased FEZF1-AS1 expression promoted gastric cancer cell proliferation in vitro. Additionally, FEZF1-AS1 was upregulated in chemo-resistant GC tissues. The regulatory effect of FEZF1-AS1 on multi-drug resistance (MDR) in GC cells and the underlying mechanism was investigated. It was found that increased FEZF1-AS1 expression promoted chemo-resistance of GC cells. Molecular interactions were determined by RNA immunoprecipitation (RIP) and the results showed that FEZF1-AS1 regulated chemo-resistance of GC cells through modulating autophagy by directly targeting ATG5. The proliferation and autophagy of GC cells promoted by overexpression of LncFEZF1-AS1 was suppressed when ATG5 was knocked down. Moreover, knockdown of FEZF1-AS1 inhibited tumor growth and increased 5-FU sensitivity in GC cells in vivo. Taken together, this study revealed that the FEZF1-AS1/ATG5 axis regulates MDR of GC cells via modulating autophagy.

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.

Identification of a novel molecule target for the diagnosis, prediction, and treatment of hepatic metastasis of gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 53-53
Author(s):  
Mitsuro Kanda ◽  
Haruyoshi Tanaka ◽  
Takashi Miwa ◽  
Daisuke Kobayashi ◽  
Chie Tanaka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Hepatic Metastasis ◽  
Clinicopathological Parameters ◽  
Gastric Cancer Cells ◽  
Expression Levels ◽  
Hepatic Recurrence ◽  
Cancer Tissues

53 Background: Hepatic metastasis of gastric cancer has become a growing issue, because effective treatment and specific biomarkers are not available. The aim of this study was to identify a molecule mediating hepatic metastasis, which serves as a diagnostic marker, and to determine its potential as a therapeutic target. Methods: Stable knockdown gastric cancer cells were established using genome editing technique and cell activities were compared to control cells in vitro and in vivo. Tissue expression levels of the candidate molecule were evaluated in 300 patients with gastric cancer and correlated to clinicopathological parameters including patterns of metastasis and recurrences. Results: Global expression analysis revealed that synaptotagmin VII (SYT7) was overexpressed in gastric cancer tissues with hepatic metastasis. Gastric cancer cell lines differentially expressed high levels of SYT7 that positively correlated with those of SNAI1 and TGFB3, and inversely with RGS2. Stable knockout of SYT7 inhibited the proliferation of gastric cancer cells, indicated by increased apoptosis, and decreased cell migration, invasion, and adhesion abilities. The tumorigenicity of SYT7 knockout cells was moderately reduced in a mouse subcutaneous model and more strikingly decreased in a hepatic metastasis model. The protein expression levels of BCL2 and HIF1A were decreased in tumors formed by SYT7 knockout cells, and SYT7 levels in primary gastric cancer tissues were significantly associated with hepatic recurrence, metastasis, and adverse prognosis. Conclusions: SYT7 serves as a target for treating hepatic metastasis of gastric cancer as well as a diagnostic tool.

scholarly journals Tenascin-c Knockdown Suppresses Vasculogenic Mimicry of Gastric Cancer by Inhibiting ERK- Triggered EMT

2021 ◽  
Author(s):  
Xing Kang ◽  
en xu ◽  
Xingzhou wang ◽  
Lulu Qian ◽  
Zhi Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Vasculogenic Mimicry ◽  
Gastric Cancer Cells ◽  
Tenascin C ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract BackgroundGastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. Tenascin-c (TNC) plays a pivotal role in VM. Thus, we explored the role of TNC in VM formation in gastric cancer.MethodsGastric cancer tissues and corresponding adjacent tissues were collected from gastric cancer patients after surgery. We used western blot and immunohistochemistry to examine the expression of TNC in tissues and used siRNA and lentivirus to knockdown the TNC expression in gastric cancer cell lines. Then three-dimensional culturing, CCK-8, Edu assay, flow cytometry, trasnwell and pseudopodia formation assay were used to evaluate the function of TNC in gastric cancer cells and bioinformatic prediction was used to explore the mechanism underlying TNC modulating the VM in gastric cancer. Xenograft and peritoneal dissemination model were used to further explore the role of TNC in vivo.ResultsIn this study, we demonstrated that TNC was highly expressed in gastric cancer tissues and correlated with poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. What’s more, rescue experiments showed that activation of p-ERK could reverse the suppressive role of TNC knockdown in gastric cancer cells.ConclusionsTNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease anti-angiogenic therapeutic resistance.

scholarly journals Knockdown of Kremen2 Inhibits Tumor Growth and Migration in Gastric Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Beibei Chen ◽  
Sai-Qi Wang ◽  
Jinxi Huang ◽  
Weifeng Xu ◽  
Huifang Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Gastric Cancer Cells ◽  
And Migration ◽  
Induced Apoptosis ◽  
Gastric Cancer Patients

Kremen2 (Krm2) plays an important role in embryonic development, bone formation, and tumorigenesis as a crucial regulator of classical Wnt/β-catenin signaling pathway. However, the role of Krm2 in gastric cancer is not clear. The aim of this study was to explore the regulatory role of Krm2 in the tumorigenesis and metastasis of gastric cancer. It was demonstrated that, compared to para-cancerous tissues, Krm2 was significantly up-regulated in gastric cancer tissues and was positively correlated with the pathological grade of gastric cancer patients. Given that Krm2 is abundantly expressed in most tested gastric cancer cell lines, Krm2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down Krm2, both the cell survival in vitro and tumorigenesis in vivo of gastric cancer cells were inhibited. At the same time, knockdown of Krm2 induced apoptosis, cell cycle arrest at G2/M phase and repression of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of Krm2 suppressed PI3K/Akt pathway. Therefore, we revealed the novel role and the molecular mechanism of Krm2 in promoting the tumorigenesis and metastasis in gastric cancer. Krm2 can be a potent candidate for designing of targeted therapy.

scholarly journals Knockdown of PD-L1 in Human Gastric Cancer Cells Inhibits Tumor Progression and Improves the Cytotoxic Sensitivity to CIK Therapy

2017 ◽  
Vol 41 (3) ◽  
pp. 907-920 ◽  
Author(s):  
Jing Li ◽  
Lujun Chen ◽  
Yuqi Xiong ◽  
Xiao Zheng ◽  
Quanqin Xie ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Over Expression ◽  
Gastric Cancer Cell Lines ◽  
Cancer Tissues

Background/Abstract: PD-L1 has been an important target of cancer immunotherapy. We have showed that in human gastric cancer tissues, over-expression of PD-L1 was significantly associated with cancer progression and patients’ postoperative prognoses. However, as of now, how PD-L1 regulates the biological function of gastric cancer cells still remains elusive. Methods: We constructed the stable PD-L1 knockdown expression gastric cancer cell lines by using RNAi method, and further investigated the changes of biological functions including cell viability, migration, invasion, cell cycle, apoptosis, tumorigenicity in vivo, and the cytotoxic sensitivity to CIK therapy, in contrast to the control cells. Results: In the current study, we demonstrated that the knockdown of PD-L1 expression in human gastric cancer cells could significantly suppress the cell proliferation, migration, invasion, apoptosis, cell cycle, tumorigenicity in vivo and the cytotoxic sensitivity to CIK therapy. Conclusion: Our results indicate that PD-L1 contributes towards transformation and progression of human gastric cancer cells, and its intervention could prove to be an important therapeutic strategy against gastric cancer.

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