scholarly journals Restoration of klotho gene expression induces apoptosis and autophagy in gastric cancer cells: tumor suppressive role of klotho in gastric cancer

2013 ◽  
Vol 13 (1) ◽  
pp. 18 ◽  
Author(s):  
Biao Xie ◽  
Jianping Zhou ◽  
Guoshun Shu ◽  
Dong-cai Liu ◽  
Jiapeng Zhou ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linwen Zhu ◽  
Zhe Li ◽  
Xiuchong Yu ◽  
Yao Ruan ◽  
Yijing Shen ◽  
...  

Abstract Background Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice. Results tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth. Conclusions tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qing Li ◽  
Dachuan Zhang ◽  
Hui Wang ◽  
Jun Xie ◽  
Lei Peng ◽  
...  

Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson’s test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.


2006 ◽  
Vol 96 (1) ◽  
pp. 21-29 ◽  
Author(s):  
V. Y. Shin ◽  
W. K. K. Wu ◽  
K. M. Chu ◽  
M. W. L. Koo ◽  
H. P. S. Wong ◽  
...  

2019 ◽  
Vol 20 (19) ◽  
pp. 4709 ◽  
Author(s):  
Seong-Hun Kim ◽  
Hua Jin ◽  
Ruo Yu Meng ◽  
Da-Yeah Kim ◽  
Yu Chuan Liu ◽  
...  

The Hippo pathway is often dysregulated in many carcinomas, which results in various stages of tumor progression. Ursolic acid (UA), a natural compound that exists in many herbal plants, is known to obstruct cancer progression and exerts anti-carcinogenic effect on a number of human cancers. In this study, we aimed to examine the biological mechanisms of action of UA through the Hippo pathway in gastric cancer cells. MTT assay showed a decreased viability of gastric cancer cells after treatment with UA. Following treatment with UA, colony numbers and the sizes of gastric cancer cells were significantly diminished and apoptosis was observed in SNU484 and SNU638 cells. The invasion and migration rates of gastric cancer cells were suppressed by UA in a dose-dependent manner. To further determine the gene expression patterns that are related to the effects of UA, a microarray analysis was performed. Gene ontology analysis revealed that several genes, such as the Hippo pathway upstream target gene, ras association domain family (RASSF1), and its downstream target genes (MST1, MST2, and LATS1) were significantly upregulated by UA, while the expression of YAP1 gene, together with oncogenes (FOXM1, KRAS, and BATF), were significantly decreased. Similar to the gene expression profiling results, the protein levels of RASSF1, MST1, MST2, LATS1, and p-YAP were increased, whereas those of CTGF were decreased by UA in gastric cancer cells. The p-YAP expression induced in gastric cancer cells by UA was reversed with RASSF1 silencing. In addition, the protein levels in the Hippo pathway were increased in the UA-treated xenograft tumor tissues as compared with that in the control tumor tissues; thus, UA significantly inhibited the tumorigenesis of gastric cancer in vivo in xenograft animals. Collectively, UA diminishes the proliferation and metastasis of gastric cancer via the regulation of Hippo pathway through Rassf1, which suggests that UA can be used as a potential chemopreventive and therapeutic agent for gastric cancer.


2010 ◽  
Author(s):  
Prajna Mishra ◽  
Subramanian Senthivinayagam ◽  
Ajay Rana ◽  
Basabi Rana

2019 ◽  
Vol 17 ◽  
pp. 205873921984553
Author(s):  
Ying Guo ◽  
Li Zhang ◽  
Guangyu Zhou ◽  
Qingjie Ma ◽  
Shi Gao ◽  
...  

This study was designed to investigate the effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of AGS gastric cancer cell. siRNA Bmi-1 was transfected into human AGS gastric cancer cells by liposome (as siRNA Bmi-1 group) with negative control (as control group); the expressions of Bmi-1 and apoptosis-related genes like P21, Bax, and Bcl-2 in AGS cells were determined by Western blot method; the apoptosis of AGS cells was detected by flow cytometry double staining and Hoechst staining; and cell cycle was measured by flow cytometry. Compared with the control group, the expression of Bmi-1 in the siRNA Bmi-1 group was significantly decreased ( P < 0.05), the apoptosis rate was increased ( P < 0.05), and cell cycles were arrested at G1 phase (P < 0.05); the expression level of P21 and Bax in cells was significantly up-regulated while that of Bcl-2 down-regulated ( P < 0.05). The down regulation of Bmi-1 can inhibit the proliferation of AGS gastric cancer cell and promote its apoptosis, which takes such effects mainly by up-regulating P21 as well as Bax and down-regulating Bcl-2.


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