LINC01133 hampers the development of gastric cancer through increasing SST via binding to microRNA-576-5p

Epigenomics ◽  
2021 ◽  
Author(s):  
Leiyi Zhang ◽  
Ke Pan ◽  
Zhongkun Zuo ◽  
Fei Ye ◽  
Ding Cao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Nude Mice ◽  
Therapeutic Targets ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Tumor Bearing ◽  
New Therapeutic Targets ◽  
Low Expression ◽  
Development Of Gastric Cancer

Aim: Our study aimed at investigating how LINC01133 functions in gastric cancer (GC) progression. Materials & methods: Gain-of-function and loss-of-function approaches were applied to analyze the effects of LINC01133, microRNA-576-5p (miR-576-5p) and somatostatin (SST) on the biological behaviors of GC cells and in tumor-bearing nude mice. Results: GC tissues and cells showed low expression of LINC01133, and LINC01133 overexpression decreased malignant phenotypes of GC cells. Moreover, LINC01133 upregulated SST through binding to miR-576-5p. Overexpressing miR-576-5p or suppressing SST reversed the functions of LINC01133 in biological potentials of GC cells and tumor growth. Conclusion: LINC01133 overexpression may inhibit GC development by downregulation of miR-576-5p and upregulation of SST, which suggests new therapeutic targets for GC.

scholarly journals The effects of recombinant human GH on promoting tumor growth depend on the expression of GH receptor in vivo

2011 ◽  
Vol 211 (3) ◽  
pp. 249-256 ◽  
Author(s):  
Yan Lin ◽  
Suyi Li ◽  
Peng Cao ◽  
Lu Cheng ◽  
Ming Quan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Safety Concern ◽  
Severe Malnutrition ◽  
High Dose ◽  
Gastric Adenoma ◽  
Malignant Diseases ◽  
Gh Receptor ◽  
Tumor Bearing

Cancer-related malnutrition is a mortal threat to gastric carcinoma patients. However, conventional nutrition treatment is not effective for recovery. Recombinant human GH (rhGH) is widely accepted clinically to treat severe malnutrition caused by non-malignant diseases, but not approved to treat malignant diseases due to the safety concern. To explore the safety of rhGH on gastric cancer, we assessed the effect of rhGH on two tumor-bearing mice modelsin vivoestablished by human gastric adenoma cell lines of SGC-7901 and MKN-45. VEGF expression in tumor tissues was detected using immunohistochemistry. The expression of GH receptor (Ghr),Jak-2,Stat3,Vegf, Hif-1α, Fgf, andMmp-2was measured by RT-PCR and protein expression of STAT3, phosphorylated STAT3, VEGF, HIF-1α, and MMP-2 was measured by western blotting. The immunocytochemistry results showed that the GHR expression of SGC-7901 was strongly positive (GHR+++), while GHR expression of MKN-45 was regarded as negative (GHR−). After 14 days of rhGH treatment in SGC-7901 (GHR+++) tumor-bearing mice, we found that the tumor growth was significantly increased, and the expressions of downstream factors and VEGF were increased. However, in MKN-45 (GHR−) tumor-bearing mice, tumor growth was not significantly increased by rhGH, but tumor-free body weight was increased especially in high-dose rhGH-treated group (P<0.05). These findings suggest that the level of GHR expression is a key target that influences the effectiveness of rhGH on promoting the growth of gastric cancer and angiogenesis. rhGH may promote the activation of tumor angiogenesis factors through the Jak-2–STAT3 pathway.

scholarly journals 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis

2014 ◽  
Vol 9 (2) ◽  
pp. 739-744 ◽  
Author(s):  
SHU-LIN XIAN ◽  
WEI CAO ◽  
XIAO-DONG ZHANG ◽  
YUN-FEI LU
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Nude Mice ◽  
Human Gastric Cancer ◽  
Cancer Tumor ◽  
Inhibition Of Glycolysis

scholarly journals Hsa_Circular RNA_0001013 Exerts Oncogenice Effects in Gastric Cancer Via the microRNA-136/TWSG1 Axis

2022 ◽  
Author(s):  
Zhaofeng Gao ◽  
Lingyu Hu ◽  
Fei Chen ◽  
Chunhua He ◽  
Biwen Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Microarray Analysis ◽  
Nude Mice ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Circular Rnas

Abstract Background：Gastric cancer (GC) is one of the most principle malignant cancers in the digestive system. Moreover, the critical role of circular RNAs (circRNAs) has been identified in GC development. Methods：In this context, the purpose of research was to explore the regulatory mechanism circ_0001013, a novel circRNAs predicted by our research, in GC. The differential circRNAs and related mechanism in GC were predicted by microarray analysis. Circ_0001013, miR-136, and TWSG1 expression in GC clinical samples and cells was detected by RT-qPCR. The relationship among circ_0001013, miR-136, and TWSG was assessed by dual-luciferase reporter assay, biotin coupled probe pull-down assay, and biotin coupled miRNA capture. After gain- and loss-of-function assays in GC cells, cell proliferation, migration, invasion, and cell cycle and apoptosis were measured by EdU assay, scratch test, Transwell assay, and flow cytometry respectively. The effect of circ_0001013 on tumor growth was detected by xenograft tumor in nude mice. Results ：Microarray analysis predicted a novel circRNA, circ_0001013, was upregulated in GC, which was confirmed by RT-qPCR detection in GC tissues and cells. Besides, miR-136 was downregulated but TWSG1 was highly expressed in GC tissues. Mechanically, circ_0001013 could bind to miR-136, and miR-136 negatively targeted TWSG1 in GC cells. Silencing circ_0001013 or TWSG1 or overexpressing miR-136 decreased GC cell proliferation, migration, invasion, and cell cycle arrest and accelerated cell apoptosis. Circ_0001013 silencing decreased TWSG1 expression and inhibited transplanted tumor growth in nude mice. Conclusion：Circ_0001013 elevated TWSG1 expression by binding to miR-136, thereby exerting oncogenic effect in GC.

scholarly journals Hsa_Circular RNA_0001013 Exerts Oncogenice Effects in Gastric Cancer via the MicroRNA-136/TWSG1 Axis

2021 ◽  
Author(s):  
Zhaofeng Gao ◽  
Lingyu Hu ◽  
Fei Chen ◽  
Chunhua He ◽  
Biwen Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Microarray Analysis ◽  
Nude Mice ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Circular Rnas

Abstract Background：Gastric cancer (GC) is one of the most principle malignant cancers in the digestive system. Moreover, the critical role of circular RNAs (circRNAs) has been identified in GC development. Methods：In this context, the purpose of research was to explore the regulatory mechanism circ_0001013, a novel circRNAs predicted by our research, in GC. The differential circRNAs and related mechanism in GC were predicted by microarray analysis. Circ_0001013, miR-136, and TWSG1 expression in GC clinical samples and cells was detected by RT-qPCR. The relationship among circ_0001013, miR-136, and TWSG was assessed by dual-luciferase reporter assay, biotin coupled probe pull-down assay, and biotin coupled miRNA capture. After gain- and loss-of-function assays in GC cells, cell proliferation, migration, invasion, and cell cycle and apoptosis were measured by EdU assay, scratch test, Transwell assay, and flow cytometry respectively. The effect of circ_0001013 on tumor growth was detected by xenograft tumor in nude mice. Results ：Microarray analysis predicted a novel circRNA, circ_0001013, was upregulated in GC, which was confirmed by RT-qPCR detection in GC tissues and cells. Besides, miR-136 was downregulated but TWSG1 was highly expressed in GC tissues. Mechanically, circ_0001013 could bind to miR-136, and miR-136 negatively targeted TWSG1 in GC cells. Silencing circ_0001013 or TWSG1 or overexpressing miR-136 decreased GC cell proliferation, migration, invasion, and cell cycle arrest and accelerated cell apoptosis. Circ_0001013 silencing decreased TWSG1 expression and inhibited transplanted tumor growth in nude mice. Conclusion：Circ_0001013 elevated TWSG1 expression by binding to miR-136, thereby exerting oncogenic effect in GC.

scholarly journals Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Haiyong Zhang ◽  
Jing Wu ◽  
Jinqiu Yuan ◽  
Huafu Li ◽  
Yawei Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Nude Mice ◽  
Combined Treatment ◽  
Thioredoxin Reductase ◽  
Tumor Growth Inhibition ◽  
Gastric Cancer Cells

Abstract Background Oxaliplatin is one of the most commonly used chemotherapeutic agent for the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect and reduce the toxicity of oxaliplatin. In our previous study, we demonstrated that ethaselen (BBSKE), an inhibitor of thioredoxin reductase, effectively inhibited the growth of gastric cancer cells and promoted apoptosis in vitro. In the present study, we investigated whether BBSKE can potentiate the anti-tumor effect of oxaliplatin in gastric cancer in vivo and vitro. Methods Cellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells, organoid and tumor tissues was determined by using the endpoint insulin reduction assay. Western blot was used to analyze the expressions of the indicated proteins. Nude mice xenograft models were used to test the effects of BBSKE and oxaliplatin combinations on gastric cancer cell growth in vivo. In addition, we also used the combined treatment of BBSKE and oxaliplatin in three cases of gastric cancer Patient-Derived organoid (GC-PDO) to detect the anti-tumor effect. Results We found that BBSKE significantly enhanced oxaliplatin-induced growth inhibition in gastric cancer cells by inhibiting TrxR1 activity. Because of the inhibition of TrxR1 activity, BBSKE synergized with oxaliplatin to enhance the production of ROS and activate p38 and JNK signaling pathways which eventually induced apoptosis of gastric cancer cells. In vivo, we also found that BBSKE synergized with oxaliplatin to suppress the gastric cancer tumor growth in xenograft nude mice model, accompanied by the reduced TrxR1 activity. Remarkably, we found that BBSKE attenuated body weight loss evoked by oxaliplatin treatment. We also used three cases of GC-PDO and found that the combined treatment of BBSKE and oxaliplatin dramatically inhibited the growth and viability of GC-PDO with increased ROS level, decreased TrxR1 activity and enhanced apoptosis. Conclusions This study elucidates the underlying mechanisms of synergistic effect of BBSKE and oxaliplatin, and suggests that the combined treatment has potential value in gastric cancer therapy.

Molecular dynamics study on the inhibition mechanisms of ReACp53 peptide for p53-R175H mutant aggregation

2021 ◽  
Author(s):  
Jiangtao Lei ◽  
mengqiang Cai ◽  
Yun Shen ◽  
Dongdong Lin ◽  
Xiaohua Deng
Keyword(s):  
Molecular Dynamics ◽  
Tumor Growth ◽  
Dominant Negative ◽  
Loss Of Function ◽  
Gain Of Function

p53 mutant aggregation can lead to loss-of-function (LoF), dominant-negative (DN) and gain-of-function (GoF) effects, involving in tumor growth. Finding inhibition methods of p53 mutant aggregation is a key step for...

Synergistic effects of matrine and 5-fluorouracil on tumor growth of the implanted gastric cancer in nude mice

2005 ◽  
Vol 6 (2) ◽  
pp. 68-71 ◽  
Author(s):  
Mei Jie HU ◽  
Hui ZENG ◽  
Yun Lin WU ◽  
Yong Ping ZHANG ◽  
Shu ZHANG ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Nude Mice ◽  
Synergistic Effects
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