Glutamate dehydrogenase inhibits tumor growth in gastric cancer through the Notch signaling pathway

2019 ◽  
Vol 26 (3) ◽  
pp. 303-312
Author(s):  
You-Jun Wu ◽  
Zi-Long Hu ◽  
Shi-Dong Hu ◽  
Yu-Xuan Li ◽  
Xiao-Wei Xing ◽  
...  
Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1439
Author(s):  
Hyeon-Gu Kang ◽  
Won-Jin Kim ◽  
Myung-Giun Noh ◽  
Kyung-Hee Chun ◽  
Seok-Jun Kim

Spondin-2 (SPON2) is involved in cancer progression and metastasis of many tumors; however, its role and underlying mechanism in gastric cancer are still obscure. In this study, we investigated the role of SPON2 and related signaling pathway in gastric cancer progression and metastasis. SPON2 expression levels were found to be upregulated in gastric cancer cell lines and patient tissues compared to normal gastric epithelial cells and normal controls. Furthermore, SPON2 silencing was observed to decrease cell proliferation and motility and reduce tumor growth in xenograft mice. Conversely, SPON2 overexpression was found to increase cell proliferation and motility. Subsequently, we focused on regulatory mechanism of SPON2 in gastric cancer. cDNA microarray and in vitro study showed that Notch signaling is significantly correlated to SPON2 expression. Therefore, we confirmed how Notch signaling pathway regulate SPON2 expression using Notch signaling-related transcription factor interaction and reporter gene assay. Additionally, activation of Notch signaling was observed to increase cell proliferation, migration, and invasion through SPON2 expression. Our study demonstrated that Notch signaling-mediated SPON2 upregulation is associated with aggressive progression of gastric cancer. In conclusion, we suggest upregulated SPON2 via Notch signaling as a potential target gene to inhibit gastric cancer progression.


2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Kun Wu ◽  
Jun Zou ◽  
Chao Lin ◽  
Zhi-Gang Jie

Abstract Studies have highlighted the importance of microRNAs (miRs) in the development of various cancers, including gastric cancer (GC), a commonly occurring malignancy, accompanied by high recurrence and metastasis rate. The aim of the current study was to investigate the role of miR-140-5p in GC. Microarray expression profiles were initially employed to screen the differentially expressed gene related to GC, and the miR regulating the gene was predicted accordingly. The data obtained indicated that thymus cell antigen 1 (THY1) was differentially expressed in GC and confirmed to be a target gene of miR-140-5p. Poorly expressed miR-140-5p and highly expressed THY1 were observed in the GC tissues. SGC-7901 cells were treated with miR-140-5p mimic/inhibitor, siRNA against THY1 and siRNA against Notch1 in order to determine their regulatory roles in GC cell activities. The relationship of miR-140-5p, THY1 and the Notch signaling pathway was subsequently identified. Moreover, cell proliferation, migration, invasion and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), wound-healing, transwell assay and flow cytometry, respectively. The overexpression of miR-140-5p and silencing of THY1 resulted in a diminished expression of the Notch signaling pathway-related proteins, as well as inhibited proliferation, migration and invasion of GC cells, enhanced expression of pro-apoptotic proteins in addition to elevated apoptosis rate. Taken together, the present study suggests that miR-140-5p directly targets and negatively regulates THY1 expression and inhibits activation of the Notch signaling pathway, whereby the up-regulation of miR-140-5p inhibits development of GC, highlighting the promise of miR-140-5p as a potential target for GC treatment.


Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 2016 ◽  
Author(s):  
Wei Wei ◽  
Zhi-Peng Li ◽  
Zhao-Xiang Bian ◽  
Quan-Bin Han

Macrophages occur in polarized phenotypes, whose characteristics determine the role they play in tumor growth. The M1 phenotype macrophages promote tumoricidal responses and suppress tumor growth. Our previous study showed that a polysaccharide isolated from Radix Astragali, named RAP, was itself non-cytotoxic but induced RAW264.7 cells’ cytotoxicity against cancer cells. The current study was undertaken to determine its mechanism. Series studies was conducted to show that RAP is able to induce much higher gene expression of M1 markers, including iNOS, IL-6, TNF-a, and CXCL10, compared with the control group. When RAP-induced BMDMs were transplanted together with 4T1 tumor cells in BALB/c mice, both tumor volume and tumor weight decreased. Further studies indicated that RAP induces the Notch signaling pathway in RAW264.7 cells. The function of Notch signaling in macrophage polarization was confirmed by using γ-secretase inhibitor. These results suggested that Astragalus polysaccharide RAP induces macrophage’s polarization to M1 phenotype via the Notch signaling pathway.


2015 ◽  
Vol 23 (3) ◽  
pp. 381
Author(s):  
Ying-Cheng Zhang ◽  
Yong-Jin Li ◽  
Jun Shi ◽  
Zhi-Feng Qin ◽  
Pin-Kang Wei ◽  
...  

2009 ◽  
Vol 136 (5) ◽  
pp. A-460
Author(s):  
Hidetomo Konishi ◽  
Naoki Asano ◽  
Akira Imatani ◽  
Yutaka Kondo ◽  
Tomoyuki Koike ◽  
...  

2020 ◽  
Vol 10 ◽  
Author(s):  
Ming Wang ◽  
Huange Zhao ◽  
Juanjuan Hu ◽  
Zhen Xu ◽  
Yingying Lin ◽  
...  

2017 ◽  
Vol 119 (3) ◽  
pp. 2520-2534 ◽  
Author(s):  
Hai-Juan Xiao ◽  
Qing Ji ◽  
Lin Yang ◽  
Ren-Ting Li ◽  
Cheng Zhang ◽  
...  

2013 ◽  
Vol 1 ◽  
pp. 1-5 ◽  
Author(s):  
Marlena Brzozowa ◽  
Łukasz Mielańczyk ◽  
Marek Michalski ◽  
Łukasz Malinowski ◽  
Grażyna Kowalczyk-Ziomek ◽  
...  

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