CDX2 Inhibits Invasion and Migration of Gastric Cancer Cells by Phosphatase and Tensin Homologue Deleted from Chromosome 10/Akt Signaling Pathway

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.

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Long noncoding RNA STXBP5-AS1 inhibits cell proliferation, migration, and invasion through inhibiting the PI3K/AKT signaling pathway in gastric cancer cells

OncoTargets and Therapy ◽

10.2147/ott.s194463 ◽

2019 ◽

Vol Volume 12 ◽

pp. 1929-1936 ◽

Cited By ~ 12

Author(s):

Dongzhi Cen ◽

Hu Huang ◽

Liu Yang ◽

Kai Guo ◽

Jinshan Zhang

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathway ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Akt Signaling ◽

Migration And Invasion ◽

Akt Signaling Pathway ◽

Gastric Cancer Cells

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UFM1 suppresses invasive activities of gastric cancer cells by attenuating the expression of PDK1 through PI3K/AKT signaling

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1416-4 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 6

Author(s):

Jian-Xian Lin ◽

Xin-Sheng Xie ◽

Xiong-Feng Weng ◽

Sheng-Liang Qiu ◽

Changhwan Yoon ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Molecular Mechanisms ◽

Akt Signaling ◽

Invasion And Metastasis ◽

Gastric Cancer Cells ◽

Invasion And Migration ◽

And Migration ◽

Gastric Cancer Patients

Abstract Background UFM1 has been found to be involved in the regulation of tumor development. This study aims to clarify the role and potential molecular mechanisms of UFM1 in the invasion and metastasis of gastric cancer. Methods Expression of UFM1 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was analyzed by Western blotting, immunohistochemistry, and realtime PCR. Its correlation with the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. The effects of UFM1 on the invasion and migration of gastric cancer cells were determined by the wound and trans-well assays, and the effect of UFM1 on subcutaneous tumor formation was verified in nude mice. The potential downstream targets of UFM1 and related molecular mechanisms were clarified by the human protein kinase assay and co-immunoprecipitation technique. Results Compared with the corresponding adjacent tissues, the transcription level and protein expression level of UFM1 in gastric cancer tissues were significantly downregulated (P < 0.05). The 5-year survival rate of gastric cancer patients with low UFM1 expression was significantly lower than the patients with high UFM1 expression (42.1% vs 63.0%, P < 0.05). The invasion and migration abilities of gastric cancer cells with stable UFM1 overexpression were significantly decreased, and the gastric cancer cells with UFM1 stable knockdown showed the opposite results; similar results were also obtained in the nude mouse model. Further studies have revealed that UFM1 could increase the ubiquitination level of PDK1 and decrease the expression of PDK1 at protein level, thereby inhibiting the phosphorylation level of AKT at Ser473. Additionally, the effect of UFM1 on gastric cancer cell function is dependent on the expression of PDK1. The expression level of UFM1 can improve the poor prognosis of PDK1 in patients with gastric cancer. Conclusion UFM1 suppresses the invasion and metastasis of gastric cancer by increasing the ubiquitination of PDK1 through negatively regulating PI3K/AKT signaling.

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Effect of PI3K/Akt Signaling Pathway on PRAS40Thr246 Phosphorylation in Gastric Cancer Cells

Iranian Journal of Public Health ◽

10.18502/ijph.v48i12.3551 ◽

2020 ◽

Author(s):

Yizhuo LU ◽

Lianghui LI ◽

Guoyang WU ◽

Huiqin ZHUO ◽

Guoyan LIU ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Akt Signaling ◽

Cell Group ◽

Akt Signaling Pathway ◽

Gastric Cancer Cells ◽

Pathway Activation ◽

Related Proteins ◽

Proliferation And Invasion

Background: We aimed to investigate the effect of PI3K/Akt signaling pathway on PRAS40Thr246 phosphorylation in gastric cancer cells. Methods: The study was conducted from April 2017 to January 2018 in Zhongshan Hospital, Xiamen University, Xiamen, China. Gastric cancer cells were divided into three groups: gastric cancer cell group, LY294002 group and MK-2206 group. Specific tests were conducted accordingly. Results: Inhibition of PI3K/Akt signaling pathway activation and PRAS40Thr246 phosphorylation could inhibit proliferation and invasion and promote apoptosis of gastric cancer cells, and PRAS40Thr246 phosphorylation could activate PI3K/Akt signaling pathway. Conclusion: The levels of PI3K/Akt signaling pathway related proteins and p-PRAS40Thr246 were significantly increased in gastric cancer cells. p-PRAS40-Thr246 was able to reflect the activation of the PI3K/Akt signaling pathway, reflecting the sensitivity of the PI3K/AKT signaling pathway to inhibitors.

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