scholarly journals Knockdown of Rab9 Suppresses the Progression of Gastric Cancer Through Regulation of Akt Signaling Pathway

2020 ◽  
Vol 19 ◽  
pp. 153303382091595 ◽  
Author(s):  
Yong Zhu ◽  
Feng Shi ◽  
Meng Wang ◽  
Jian Ding
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Gastric Cancer Cell ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Phosphorylation Level ◽  
Gastric Cancer Cell Lines

Rabs have been reported to be involved in the carcinogenesis process and in the progression of cancer. However, it is unclear whether or not Rab9 is associated with the development of cancer. In the present study, we aimed to investigate the role of Rab9 in the biological functions of gastric cancer cells. The gastric cancer cell lines AGS and MKN45 were transfected with siRNA-Rab9 to block the expression of Rab9. The cell viability, proliferation, migration, invasion, and apoptosis were examined using Cell Count Kit-8, colony formation, wound healing, Transwell, and flow cytometry assays, respectively. Our data showed that silencing of Rab9 significantly inhibited the viability, proliferation, migration, and invasion abilities of AGS and MKN45 cells. Moreover, transfection with siRab9 promoted the rate of apoptosis in AGS and MKN45 cells through regulating the Bcl-2–Bax axis and the Caspase cascade. We also found that silencing of Rab9 inhibited activation of the Akt signaling pathway by downregulating the phosphorylation level of Akt. In conclusion, our data suggest that Rab9 plays an oncogenic role in the progression of gastric cancer, providing a potential target for the treatment of gastric cancer.

scholarly journals The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linwen Zhu ◽  
Zhe Li ◽  
Xiuchong Yu ◽  
Yao Ruan ◽  
Yijing Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Qrt Pcr

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.

scholarly journals METTL3 promotes the proliferation and mobility of gastric cancer cells

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Sen Lin ◽  
Jianing Liu ◽  
Wen Jiang ◽  
Peng Wang ◽  
Chao Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Apoptotic Pathway ◽  
Mechanistic Investigation

AbstractMethyltransferase-like 3 (METTL3) was originally known to be responsible for N6-methyladenosine (m6A) modification of mRNA. Recent studies have found that METTL3 plays important roles in a variety of tumors by regulating the translation of oncogenes. However, the functional and regulating mechanisms of METTL3 in human gastric cancer have not yet been understood. Here we knocked down METTL3 in human gastric cancer cell lines, AGS and MKN45, by using shRNA transfection. RT-qPCR assay and western blotting verified the effectiveness of RNA interference on mRNA and protein levels, respectively. Then we found that METTL3 knockdown inhibited cell proliferation, migration and invasion in AGS and MKN45 cells. Moreover, METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. Mechanistic investigation suggested that METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1. In conclusion, our study reveals that down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 may be a potential target for the treatment of human gastric cancer.

scholarly journals Effects of Syringic Acid on Apoptosis, Inflammation, and AKT/mTOR Signaling Pathway in Gastric Cancer Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinjin Pei ◽  
Periyannan Velu ◽  
Mohsen Zareian ◽  
Zili Feng ◽  
Annamalai Vijayalakshmi
Keyword(s):  
Gastric Cancer ◽  
Membrane Potential ◽  
Signaling Pathway ◽  
Mitochondrial Membrane ◽  
Gastric Cancer Cell ◽  
Syringic Acid ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Anti Cancer

Gastric cancer is one of the most common cancer and deadly disease worldwide. Despite substantial advances made in the treatment of gastric cancer, existing therapies still encounter bottlenecks. Chemotherapy, for instance, could lead to serious side effects, high drug resistance and treatment failure. Phytochemical-derived compounds from plants offer novel strategies as potent drug molecules in cancer therapy. Given the low toxicity and higher tolerance rate of naturally occurring compounds, the present study evaluated the effects of syringic acid on cytotoxicity, oxidative stress, mitochondrial membrane potential, apoptosis, and inflammatory responses in gastric cancer cell line (AGS). AGS cells were treated with various concentrations (5–40 μg/mL) of syringic acid for 24 h, after which cytotoxicity was analyzed. Reactive Oxygen Species (ROS), antioxidant enzyme activities, mitochondrial membrane potential (MMP, Δψm), cell morphologies, the expression of apoptotic markers and protein expression patterns were also investigated. Results indicated that syringic acid-treated cells developed anti-cancer activities by losing MMP, cell viability, and enhancing intracellular ROS. Syringic acid selectively developed apoptosis in a dose-dependent manner via enhanced regulation of caspase-3, caspase-9 and Poly ADP-ribose Polymerase (PARP) whereas decreasing the expression levels of p53 and BCL-2. Syringic acid also lowered activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) whereas Thio Barbituric Acid Reactive Substances (TBARS) increased. Syringic acid suppressed gastric cancer cell proliferation, inflammation, and induced apoptosis by upregulating mTOR via AKT signaling pathway. The study suggests syringic acid may constitute a promising chemotherapeutic candidate for gastric cancer treatment. Our study is the first report on the anti-cancer effects of syringic acid against gastric cancer cells via apoptosis, inhibition of inflammation, and the suppression of the mTOR/AKT signaling pathway.

scholarly journals Has-miR-875-5p Inhibits Tumorigenesis by Targeting USF2 via TGF-β Signaling Pathway in Gastric Cancer

2021 ◽  
Author(s):  
Shenshuo Gao ◽  
Zhikai Zhang ◽  
Xubin Wang ◽  
Yan Ma ◽  
Chensheng Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Research Direction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
New Research

Abstract Background: Gastric cancer (GC) is one of the most common malignancies, and more and more evdiences show that the pathogenesis is regulated by various miRNAs.In this study, we investigated the role of miR-875 in GC. Methods:The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA RT-PCR. The effect of miR-875-5p on GC proliferation was determined by CCK-8 proliferation assay and EDU assay. Migration and invasion were examined by transwell migration and invasion assay and wound healing assay. The interaction between miR-875-5p and its target gene USF2 was verified by a dual luciferase reporter assay. The effects of miR-875-5p in vivo were studied in xenograft nude mice models.Related proteins were detected by Western blot.Results:The results showed that miR-875-5p inhibited the proliferation, migration and invasion of gastric cancer cells in vitro, and inhibited tumorigenesis in vivo. USF2 proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracts the effects of miR-875-5p inhibitors.Overexpression of miR-875-5p can inhibit proliferation, migration, and invasion through the TGF-β signaling pathway by down-regulation of USF2 in GC, providing a new research direction for the diagnosis and targeted therapy of GC.Conclusions: MiR-875-5pcan inhibited the progression of GC by directly targeting USF2 and negatively regulating TGF-β signaling pathway.In the future, miR-875-5p is expected to be used as a potential therapeutic target for GC therapy.

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