Effect of Long Non-Coding RNA Plasmacytoma Variant Translocation 1 (PVT1) on the Regulation of SRY (Sex Determining Region Y)-Box 2 (SOX2) in Gastric Cancer

2020 ◽  
Vol 10 (8) ◽  
pp. 1213-1218
Author(s):  
Jinhe Zhou ◽  
Lingli Hu ◽  
Jianbin Huang ◽  
Zhiqing Ye
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Gastric Cancer Cell ◽  
Caspase 3 ◽  
Gastric Cancer Tissue ◽  
Tetrazolium Salt ◽  
Cancer Tissue ◽  
Mesenchymal Transition

The pathogenesis of gastric cancer (GC) is unclear, which has brought major problems in the diagnosis and treatment. LncRNAs is involved in the regulation of tumorigenesis and development. LncRNA PVT1 is abnormally expressed in various tumors, such as liver cancer and ovarian cancer. However, its role and mechanism in GC have not been clarified. The gastric cancer tissue and adjacent tissues were collected for measuring LncRNA PVT1 level by Real-time PCR. The gastric cancer cell line SGC-7901 was cultured in vitro and divided into control group, scramble group, and PVT1 siRNA group. The tetrazolium salt (MTT) colorimetric assay was to analyze cell proliferation. Caspase 3 activity was tested to assess cell apoptosis. Transwell chamber assay was adopted to evaluated cell invasion. Western Blot was for measuring the epithelial-mesenchymal transition (EMT) molecular proteins and SOX2. Significantly upregulated LncRNA PVT1 was found in gastric cancer tissue (P < 0 05) which was associated tumor differentiation and stage and lymph node metastasis (P < 0 05). LncRNA PVT1 siRNA transfection in SGC-7901 significantly downregulated LncRNA PVT1 expression, inhibited tumor cell proliferation, enhanced Caspase 3 activity, restrained gastric cancer cell invasion, elevated E-cadherin level, reduced Vimentin expression, and declined SOX2 expression (P < 0 05). LncRNA PVT1 is upregulated in gastric cancer and related to the clinical pathology. Downregulation of LncRNA PVT1 inhibits cell proliferation, invasion, and EMT by regulating SOX2, thereby delaying the progression of gastric cancer.

scholarly journals Long Noncoding RNA H19/miR-675 Axis Promotes Gastric Cancer via FADD/Caspase 8/Caspase 3 Signaling Pathway

2017 ◽  
Vol 42 (6) ◽  
pp. 2364-2376 ◽  
Author(s):  
Jin Yan ◽  
Yifeng Zhang ◽  
Qiang She ◽  
Xuan Li ◽  
Lei Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Gastric Cancer Cell ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Gastric Cancer Cell Lines

Background: Long noncoding RNA (lncRNA) H19 is emerging as a vital regulatory molecule in the progression of different types of cancer and miR-675 is reported to be embedded in H19's first exon. However, their function and specific mechanisms of action have not been fully elucidated. The aim of this study was to identify a novel lncRNA-microRNA-mRNA functional network in gastric cancer. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the relative expression of H19 and miR-675 in normal (GES-1) and gastric cancer cell lines (SGC-7901, SGC-7901/DDP) as well as in tumor tissues. Gain and loss of function approaches were carried out to investigate the potential roles of H19/miR-675 in cell proliferation and apoptosis. Moreover, Fas associated via death domain (FADD) was validated to be the target of miR-675 via luciferase reporter assay. Western blotting was used to evaluate the protein expression of related signaling pathway. Results: In our study H19 and miR-675 were increased in gastric cancer cell lines and tissues. Overexpression of H19 and miR-675 promoted cell proliferation and inhibited cell apoptosis, whereas knockdown of H19 and miR-675 inhibited these effects. By further examining the underlying mechanism, we showed that H19/miR-675 axis inhibited expression of FADD. FADD downregulation subsequently inhibited the caspase cleavage cascades including caspase 8 and caspase 3. Conclusion: Taken together, our results point to a novel regulatory pathway H19/miR-675/ FADD/caspase 8/caspase 3 in gastric cancer which may be potential target for cancer therapy.

scholarly journals Gastric cancer cell proliferation is inhibited by α-santonin via targeting of PI3K and AKT activation

2020 ◽  
Vol 19 (4) ◽  
pp. 765-771
Author(s):  
Lin Nie ◽  
Lijiu Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Gastric Cancer Cell ◽  
Population Increase ◽  
Control Treatment ◽  
Cancer Cell Proliferation ◽  
Gastric Cancer Cell Proliferation ◽  
And Migration

Purpose: To investigate the effect of α-santonin on proliferation of gastric cancer cells.Methods: Cell proliferation was analysed by 3-4-5-Dimethylthiazol-2-yl-25-diphenyltetrazolium bromide (MTT) assay and migration by wound healing assay. Matrigel coated Transwell chamber was used for determination of cell invasion. Expression of proteins and mRNA was assessed using western blot and RT-PCR assay, respectively.Results: In NUGC4 and MKN45 cell cultures, treatment with α-santonin promoted miR 145 expression significantly when compared to control. Treatment of NUGC4 cells with α-santonin for 48 h significantly increased apoptosis in comparison to control. At 100, 150 and 200 μM concentrations of α-santonin, the level of cell apoptosis increased to 45, 53 and 64 %, respectively (p < 0.05). Treatment with α-santonin caused NUGC4 cell population increase in G1/G0 phase with reduction in S and G2/M phases. A significant reduction in NUGC4 cell invasion was observed following treatment with α-santonin. The α- santonin treatment of NUGC4 cells at 200 μM concentration markedly reduced cell invasion (p < 0.05). Treatment of NUGC4 cells with α-santonin reduced the expression of c Myc, PI3K, and p AKT. The production of MMP-2 and MMP-9 in NUGC4 cells was also decreased by α-santonin treatment.Conclusion: The study demonstrates that α-santonin plays important role in inhibition of gastric cancer cell proliferation by arrest of cell cycle and apoptosis induction. Moreover, the activation of PI3K and AKT was also suppressed by α-santonin. Therefore, α-santonin can potentially be used for the treatment of gastric cancer. Keywords: Apoptosis, MicroRNA, Tumor suppressor, Metastasis, Infiltration

Single-chain Antibody Against Reg4 Suppresses Gastric Cancer Cell Growth and Enhances 5-FU-induced Cell Death in vitro

2019 ◽  
Vol 19 (5) ◽  
pp. 610-619 ◽  
Author(s):  
Xue-Qing Zhang ◽  
Lu-Ting Yu ◽  
Pei Du ◽  
Tian-Qi Yin ◽  
Zhi-Yuan Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Ags Cells ◽  
Thiazolyl Blue Tetrazolium Bromide

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.

Sign in / Sign up

Export Citation Format

Share Document