Latent membrane protein 2A inhibits expression level of Smad2 through regulating miR‐155‐5p in EBV‐associated gastric cancer cell lines

2019 ◽  
Vol 92 (1) ◽  
pp. 96-106 ◽  
Author(s):  
Qianzhu Shi ◽  
Yan Zhang ◽  
Wen Liu ◽  
Hua Xiao ◽  
Yifan Qi ◽  
...  
2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15571-e15571
Author(s):  
Zhi-Qiang Ling

e15571 Background: Therapies targeted to the immune checkpoint mediated by PD-1 and PD-L1 show antitumor activity in some solid tumors. We have now examined PD-L1 expression and its regulation in gastric cancer with p-PAQR3Thr32 protein. Methods: The expression of PD-L1 at the protein and mRNA levels in gastric cancer cell lines was examined by flow cytometry, real-time RT-PCR and western blot analysis, respectively. The expression of PD-L1 and p-PAQR3Thr32 protein in 319 surgically resected gastric cancer specimens was evaluated by immunohistochemical analysis. Results: The PD-L1 expression level was higher in gastric cancer cell lines positive for p-PAQR3Thr32 protein induced by glucose starvation than in those negative for the p-PAQR3Thr32 protein. Forced expression of p-PAQR3Thr32 protein in gastric cancer cells markedly increased PD-L1 expression, whereas endogenous PD-L1 expression in p-PAQR3Thr32 protein positive gastric cancer cells was attenuated by treatment with PAQR3 siRNAs. Furthermore, expression of PD-L1 was downregulated by inhibitors of the IRF1 and STAT1 in IFNs-PDL1 signaling pathway in gastric cancer cells positive for p-PAQR3Thr32 protein. At clinical tissue level, the expression level of PD-L1 was positively associated with the presence of p-PAQR3Thr32 protein in gastric cancer specimens. Moreover, the expression level of p-PAQR3Thr32 protein was negatively correlated with CD3, CD8, GZMA (CD8 T cell secretory factor) and positively correlated with CD68 (macrophage marker). Conclusions: Our findings that p-PAQR3Thr32 protein induced by glucose deficiency upregulate PD-L1 by activating IFNs-PDL1 signaling pathway in gastric cancer reveal a direct link between p-PAQR3Thr32 protein and PD-L1 expression. It is suggested that p-PAQR3Thr32 protein may be involved in tumor immunosuppression by inhibiting the proliferation and activity of CD8 T cells in gastric cancer tissues.


2019 ◽  
Vol 19 (3) ◽  
pp. 304-309 ◽  
Author(s):  
Najibeh Shekari ◽  
Faezeh Asghari ◽  
Navideh Haghnavaz ◽  
Dariush Shanehbandi ◽  
Vahid Khaze ◽  
...  

Background: MicroRNAs are noncoding RNAs which play critical roles in response to anti-cancer agents. Let-7a and miR-21 are well-known tumor-suppressor and oncomiR miRNAs, respectively. They are involved in tumorigenesis of gastric cancer and have potential to be used as markers in response to the therapy. Objective: We aimed to study alterations in the expression of Let-7a and miR-21, and their targets in gastric cancer cell lines after treatment with docetaxel. Methods: In order to determine the IC50 of docetaxel, MTT assay was performed in AGS, MKN45 and KATO III gastric cancer cell lines. The expression levels of Let-7a and miR-21 and their target genes, HMGA2 and PDCD4, were determined by reverse-transcription quantitative real-time PCR for both treated and untreated cell lines. Results: MTT assay showed higher IC50 concentration of docetaxel in KATO III in comparison with AGS and MKN45, indicating KATO III`s higher resistance to docetaxel. Following the treatment, the expression level of Let-7a was significantly increased in AGS and MKN45, while decreased in KATO III. Expression level of miR- 21 in the three treated cell lines was increased significantly. Not only Let-7a, but also expression level of HMGA2 and PDCD4 genes showed different patterns in KATO III in comparison with AGS and MKN45. Conclusion: Down-regulation and up-regulation of Let-7a in docetaxel-resistant and sensitive cell lines, respectively indicates its potential usefulness as biomarker for responsiveness of gastric cancer to the therapy with docetaxel and also for predicting patient`s outcome.


2009 ◽  
Vol 155 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Hideyo Miyato ◽  
Joji Kitayama ◽  
Hiroharu Yamashita ◽  
Daisuke Souma ◽  
Masahiro Asakage ◽  
...  

Digestion ◽  
2006 ◽  
Vol 74 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Jinyu Gu ◽  
Hirofumi Yamamoto ◽  
Xueying Lu ◽  
Chew Yee Ngan ◽  
Tadashi Tsujino ◽  
...  

2015 ◽  
Vol 11 (1) ◽  
pp. 63
Author(s):  
Shang-Jin Peng ◽  
Jue-Wei Chen

<p class="Abstract">The present study investigates the effect of rubriflordilactone A on the viability and its underlying mechanism in gastric cancer cell lines (SNU-1 and SNU-5) and normal gastric epithelial cell line (GES‑1). Incubation of the gastric cancer and non cancer cell lines in acidic media led to reduction in the viability of the non cancer cells without any effect on cancer cells. Apoptosis in SNU-1 and SNU-5 cells was induced on exposure to rubriflordilactone A after 48 hours compared to the control cells (p&lt;0.01). The percentage of apoptosis in SNU-1 and SNU-5 cells on exposure to rubriflordilactone A was 79.3 ± 4.7 and 74.0 ± 5.1, respectively after 48 hours. Exposure of SNU-1 and SNU-5 cancer cell lines to rubriflordilactone A at a concentration of 10 μM in media with acidic pH decreased phosphorylation of ERK ½. The similar reduction was caused by ERK 1/2 phosphorylation inhibition, PD98059. Thus rubriflordilactone A reduces viability of gastric cancer cell lines by inducing apoptosis through the reduction of ERK 1/2 phosphorylation.</p><p> </p>


2001 ◽  
Vol 32 (1) ◽  
pp. 67-81 ◽  
Author(s):  
Yun-Ling Zheng ◽  
Alison M. Herr ◽  
Blake A. Jacobson ◽  
Lance J. Ferrin

2016 ◽  
Vol 143 (4) ◽  
pp. 573-600 ◽  
Author(s):  
Julia Kneissl ◽  
Anja Hartmann ◽  
Nicole Pfarr ◽  
Franziska Erlmeier ◽  
Thomas Lorber ◽  
...  

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