scholarly journals Inhibiting PP2Acα Promotes the Malignant Phenotype of Gastric Cancer Cells through the ATM/METTL3 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Zhaoxiang Cheng ◽  
Shan Gao ◽  
Xiaojie Liang ◽  
Chao Lian ◽  
Jianquan Chen ◽  
...  

This article is aimed at exploring the relationship between the phosphatase 2A catalytic subunit Cα (PP2Acα, encoded by PPP2CA) and methyltransferase-like 3 (METTL3) in the malignant progression of gastric cancer (GC). Through analyzing the bioinformatics database and clinical tissue immunohistochemistry results, we found that abnormal PP2Acα and METTL3 levels were closely related to the malignant progression of GC. To explore the internal connection between PP2Acα and METTL3 in the progression of GC, we carried out cellular and molecular experiments and finally proved that PP2Acα inhibition can upregulate METTL3 levels by activating ATM activity, thereby promoting the malignant progression of GC.

Author(s):  
Yangmei Zhang ◽  
Xichang Zhou ◽  
Long Cheng ◽  
Xiang Wang ◽  
Qinglin Zhang ◽  
...  

PRKAA1 (protein kinase AMP-activated catalytic subunit α 1) is a catalytic subunit of AMP-activated protein kinase (AMPK), which plays a key role in regulating cellular energy metabolism through phosphorylation, and genetic variations in the PRKAA1 have been found to be associated with gastric cancer risk. However, the effect and underlying molecular mechanism of PRKAA1 on gastric cancer tumorigenesis, especially the proliferation and apoptosis, are not fully understood. Our data showed that PRKAA1 is highly expressed in BGC-823 and MKN45 cells and is expressed low in SGC-7901 and MGC-803 cells in comparison with the other gastric cancer cells. PRKAA1 downregulation by shRNA or treatment of AMPK inhibitor compound C significantly inhibited proliferation as well as promoted cell cycle arrest and apoptosis of BGC-823 and MKN45 cells. Moreover, the expression of PCNA and Bcl-2 and the activity of JNK1 and Akt signaling were also reduced in BGC-823 and MKN45 cells after PRKAA1 downregulation. In vivo experiments demonstrated that tumor growth in nude mice was significantly inhibited after PRKAA1 silencing. Importantly, inactivation of JNK1 or Akt signaling pathway significantly inhibited PRKAA1 overexpression-induced increased cell proliferation and decreased cell apoptosis in MGC-803 cells. In conclusion, our findings suggest that PRKAA1 increases proliferation and restrains apoptosis of gastric cancer cells through activating JNK1 and Akt pathways.


Author(s):  
Jianmiao WANG ◽  
Jing YANG ◽  
Ji QIU ◽  
Taoyan SONG

Background: We aimed to investigate the relationship between miR-596, BCL-2, and apoptosis of gastric cancer cells, and to explore the mechanism of miR-596 in gastric cancer. Besides, this study aimed to find the target of miR-596 and explore the mechanism of action of miR-596 in gastric cancer. Methods: Eighteen samples of gastric cancer tissues and 18 samples of corresponding tumor-adjacent tissues were collected from 18 gastric cancer patients (aged from 40 to 55 yr) admitted to Zhuji People's Hospital, Zhuji, China from March 2017 to May 2018. The expression levels of miR-596 and BCL-2 were detected to verify the regulation of miR-596 on the apoptosis and proliferation of gastric cancer cell lines MKN-45 and HGC-27 and its effect on BCL-2 expression. Results: The expression level of miR-596 was notably lower in gastric cancer tissues than in adjacent tissues, and BCL-2 level was notably higher in gastric cancer tissues than in adjacent tissues. After the up-regulation of miR-596 expression, the proliferation of MKN-45 and HGC-27 cells was significantly decreased, the level of apoptosis was significantly increased (P<0.05), and the expression of BCL-2 was decreased. The dual-luciferase report showed that miR-596 had a targeting inhibition of BCL-2. Gastric cancer cells with up-regulated miR596 and BCL-2 had significantly higher proliferation and lower apoptosis than cells with up-regulated miR-596. Conclusions: miR-596 can inhibit the proliferation of gastric cancer cells and promote the apoptosis through its targeting inhibition of BCL-2 expression.


Oncotarget ◽  
2017 ◽  
Vol 8 (65) ◽  
pp. 108610-108623 ◽  
Author(s):  
Junzhong Lai ◽  
Hanze Wang ◽  
Qianping Luo ◽  
Shanlu Huang ◽  
Shujin Lin ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xiaoying Guan ◽  
Xiaoli Guan ◽  
Junjie Qin ◽  
Long Qin ◽  
Wengui Shi ◽  
...  

The mechanism underlying the poor prognosis of gastric cancer, including its high degree of malignancy, invasion, and metastasis, is extremely complicated. Rho GTPases are involved in the occurrence and development of a variety of malignant tumors. ARHGAP11A, in the Rho GTPase activating protein family, is highly expressed in gastric cancer, but its function and mechanism have not yet been explored. In this study, the effect of ARHGAP11A on the occurrence and development of gastric cancer and the mechanism related to this effect were studied. The expression of ARHGAP11A was increased in gastric cancer cells and tissues, and high ARHGAP11A expression in tissues was related to the degree of tumor differentiation and poor prognosis. Moreover, ARHGAP11A knockout significantly inhibited cell proliferation, cell migration, and invasion in vitro and significantly inhibited the tumorigenic ability of gastric cancer cells in nude mice in vivo. Further studies revealed that ARHGAP11A promotes the malignant progression of gastric cancer cells by interacting with TPM1 to affect cell migration and invasion and the stability of actin filaments. These results suggest that ARHGAP11A plays an important role in gastric cancer and may become a useful prognostic biomarker and therapeutic target for gastric cancer patients.


1998 ◽  
Vol 34 (7) ◽  
pp. 1117-1123 ◽  
Author(s):  
Y Kato ◽  
Y Nagashima ◽  
N Koshikawa ◽  
Y Miyagi ◽  
H Yasumitsu ◽  
...  

2004 ◽  
Vol 10 (18) ◽  
pp. 6239-6247 ◽  
Author(s):  
Na Liu ◽  
Feng Bi ◽  
Yanglin Pan ◽  
Lijun Sun ◽  
Yan Xue ◽  
...  

2013 ◽  
Vol 14 (1) ◽  
pp. 173-177 ◽  
Author(s):  
Min Xu ◽  
Fa-Le Cao ◽  
Nai-Yi Li ◽  
Yong-Qiang Liu ◽  
Yan-Peng Li ◽  
...  

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