scholarly journals miR-34a mimic or pre-mir-34a, which is the better option for cancer therapy? KatoIII as a model to study miRNA action in human gastric cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Narjes Jafari ◽  
Saeid Abediankenari ◽  
Hadi Hossein-Nataj
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Therapeutic Option ◽  
Transient Transfection ◽  
Regulatory Function ◽  
Human Gastric Cancer ◽  
Stable Transfection ◽  
Apoptotic Cells ◽  
Mrna Levels ◽  
Gastric Cancer Cells

Abstract Background Aberrantly expressed microRNAs play important roles in gastric tumorigenesis. However, use of miRNAs as a therapeutic option in gastric cancer still remains as a challenging problem. Methods We performed transient transfection of miR-34a-5p mimic and stable transfection of pre-mir-34a into KatoIII cells. Then, we evaluated the effect of transfected miRNAs on numerous cellular and molecular processes. Results Following transient transfection of miR-34a-5p mimic at 25 nM—a commonly used concentration—into KatoIII cells, inhibition of two target genes expression, namely Notch1 and β-catenin, was not observed, but a non-significant marginal increase of these genes was detected. No changes were detected in the percentage of apoptotic cells as well as in CD44 + and EpCAM + cells after 25 nM miR-34a-5p mimic transfection. Interestingly, stable transfection of pre-mir-34a into KatoIII cells (named as KatoIII-pGFPC1-34a cells) caused a significant repression in β-catenin protein and Notch1 mRNA levels (p < 0.05 and p < 0.01, respectively) relative to equivalent control (KatoIII- pGFPC1-empty cells). The percentage of CD44 + cells in the KatoIII-pGFPC1-34a cells (< 40%) was significantly lower than that in control cells (~ 95%) (p < 0.05). An increase of ~ 3.5% in apoptotic cells and a slower proliferation rate were detected in KatoIII-pGFPC1-34a cells. Conclusions Our study revealed that the effect of miR mimic in target gene repression can be dependent to its concentration as well as to the cell type. Meanwhile, our findings further support a regulatory function for pre-miRNAs in target repression and will help to develop effective therapeutic strategies in cancer treatment.

scholarly journals MyoD1 suppresses cell migration and invasion by inhibiting FUT4 transcription in human gastric cancer cells

2019 ◽  
Vol 27 (10-11) ◽  
pp. 773-784 ◽  
Author(s):  
Fei Wu ◽  
Yannan Qin ◽  
Qiuyu Jiang ◽  
Jinyuan Zhang ◽  
Fang Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Target Genes ◽  
Myogenic Differentiation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion ◽  
Chip Sequencing

AbstractMyogenic differentiation 1 (MyoD1) is a transcription factor that promotes expression of muscle-specific genes. MyoD1 is expressed at significantly lower levels in gastric cancer (GC) tissues and cells, and it induces apoptosis in GC cells. However, functions for MyoD1 in GC cell migration and gene expression have not been documented. We show that knockdown of MyoD1 promoted migration and invasion of GC cells, whereas MyoD1 overexpression suppressed migration and invasion. We performed chromatin immunoprecipitation (ChIP)-sequencing to identify MyoD1 target genes in MKN-45 cells. The 2-kb upstream regions (Up2k) of the transcription start sites of 57 genes were probably bound by MyoD1. Six of these genes function in signaling pathways such as synthesis of glycosphingolipid biosynthesis—lacto and neolacto series. MyoD1 inhibited transcription of fucosyltransferase IV (FUT4) by binding directly to the FUT4 F3; this finding was validated by ChIP-quantitative PCR and a luciferase reporter assay. Ulex europaeus agglutinin I, which binds Fucα1-2Galβ1-4GlcNAc, and Lewis antigens showed decreased binding to the plasma membrane of cells that overexpressed MyoD1. Knockdown of FUT4 mimicked MyoD1 overexpression by suppressing GC cell migration and invasion; this result implied that MyoD1 suppressed cell migration and invasion via inhibiting the FUT4/matrix metallopeptidase signaling pathway. In summary, this study demonstrated that MyoD1 suppresses migration and invasion of GC cells by directly binding to the F3 region in the FUT4 Up2k and inhibiting FUT4/type II Lewis antigen expression.

IRTKS is correlated with progression and survival time of patients with gastric cancer

Gut ◽  
2017 ◽  
Vol 67 (8) ◽  
pp. 1400-1409 ◽  
Author(s):  
Li-Yu Huang ◽  
Xuefei Wang ◽  
Xiao-Fang Cui ◽  
He Li ◽  
Junjie Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Time ◽  
Target Genes ◽  
Human Gastric Cancer ◽  
Wild Type ◽  
Gastric Cancer Cells ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Background and objectivesIRTKS functions as a novel regulator of tumour suppressor p53; however, the role of IRTKS in pathogenesis of gastric cancer is unclear.DesignWe used immunohistochemistry to detect IRTKS levels in 527 human gastric cancer specimens. We generated both IRTKS-deficient and p53-deficient mice to observe survival time of these mice and to isolate mouse embryonic fibroblasts (MEFs) for evaluating in vivo tumorigenicity. Co-immunoprecipitation was used to study the interaction among p53, MDM2 and IRTKS, as well as the ubiquitination of p53.ResultsIRTKS was significantly overexpressed in human gastric cancer, which was conversely associated with wild-type p53 expression. Among patients with wild-type p53 (n=206), those with high IRTKS expression (n=141) had a shorter survival time than those with low IRTKS (n=65) (p=0.0153). Heterozygous p53+/− mice with IRTKS deficiency exhibited significantly delayed tumorigenesis and an extended tumour-free survival time. p53+/− MEFs without IRTKS exhibited attenuated in vivo tumorigenicity. IRTKS depletion upregulated p53 and its target genes, such as BAX and p21. Intriguingly, IRTKS overexpression promoted p53 ubiquitination and degradation in MEFs and gastric cancer cells. Under DNA damage conditions, IRTKS was phosphorylated at Ser331 by the activated Chk2 kinase and then dissociated from p53, along with the p53-specific E3 ubiquitin ligase MDM2, resulting in attenuated p53 ubiquitination and degradation.ConclusionIRTKS overexpression is negatively correlated with progression and overall survival time of patients with gastric cancer with wild-type p53 through promotion of p53 degradation via the ubiquitin/proteasome pathway.

scholarly journals Resveratrol Analog 4-Bromo-Resveratrol Inhibits Gastric Cancer Stemness through the SIRT3-c-Jun N-Terminal Kinase Signaling Pathway

2021 ◽  
Vol 44 (1) ◽  
pp. 63-72
Author(s):  
Yun-Shen Tai ◽  
Yi-Shih Ma ◽  
Chun-Lin Chen ◽  
Hsin-Yi Tsai ◽  
Chin-Chuan Tsai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Therapeutic Option ◽  
Mitochondrial Protein ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Therapeutic Drugs ◽  
Gastric Cancer Treatment ◽  
Gastric Cancer Stem Cells

Chemotherapy is the treatment of choice for gastric cancer, but the currently available therapeutic drugs have limited efficacy. Studies have suggested that gastric cancer stem cells may play a key role in drug resistance in chemotherapy. Therefore, new agents that selectively target gastric cancer stem cells in gastric tumors are urgently required. Sirtuin-3 (SIRT3) is a deacetylase that regulates mitochondrial metabolic homeostasis to maintain stemness in glioma stem cells. Targeting the mitochondrial protein SIRT3 may provide a novel therapeutic option for gastric cancer treatment. However, the mechanism by which stemness is regulated through SIRT3 inhibition in gastric cancer remains unknown. We evaluated the stemness inhibition ability of the SIRT3 inhibitor 4′-bromo-resveratrol (4-BR), an analog of resveratrol in human gastric cancer cells. Our results suggested that 4-BR inhibited gastric cancer cell stemness through the SIRT3-c-Jun N-terminal kinase pathway and may aid in gastric cancer stem-cell–targeted therapy.

scholarly journals The p62/Keap1/Nrf2 axis in the control of C-2 induced human gastric cancer cell death switching between autophagy and apoptosis

2021 ◽  
Author(s):  
ZhenYa Wang ◽  
Yong Guo ◽  
En Zhang ◽  
QianHong Ban ◽  
MengLin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Target Genes ◽  
Beclin 1 ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Compound C ◽  
Anti Cancer ◽  
Cancer Activity

Abstract Background Compound C-2 is a derivative of natural product Jaspine B and possesses anti-cancer activity against bladder cancer cells. However, little is known about its anti-cancer activity against gastric cancer. In this research, mechanism underlying anti-cancer effect of C-2 in gastric cancer cells was well investigated. Methods Anti-cancer activities of C-2 were determined by MTT, western blotting and flow cytometry. A serial of specific inhibitors, immunoprecipitation, siRNA and immunofluorescence were utilized to explore signaling pathways affected by C-2. Results C-2 induces apoptosis in gastric cancer cells through the internal mitochondrial pathway, and triggers autophagy in gastric cancer cells through JNK/ERK pathway. Phosphorylated JNK/ERK further activates Beclin1 via disturbing Beclin-1/Bcl-xL or Beclin-1/Bcl-2 complexes, leading to autophagy and up-regulated p62. Next, p62 competitively binds keap1 to release Nrf2, thus promoting translocation of Nrf2 from cytoplasm to nucleus and triggering expression of Nrf2 target genes. Pharmacological inhibition or knockdown of key proteins in autophagy attenuates C-2 induced cell apoptosis, indicating that autophagy antagonizes cell apoptosis induced by C-2. Conclusion C-2 possesses anti-tumor activity against gastric cancer cells, while C-2 triggered-autophagy antagonizes cell arrest and apoptosis induced by C-2 by upregulating Nrf2 in nucleus.

Helicobacter pyloriinduces Snail expression through ROS-mediated activation of Erk and inactivation of GSK-3β in human gastric cancer cells

2016 ◽  
Vol 55 (12) ◽  
pp. 2236-2246 ◽  
Author(s):  
Hoang-Kieu-Chi Ngo ◽  
Hee Geum Lee ◽  
Juan-Yu Piao ◽  
Xiancai Zhong ◽  
Ha-Na Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Snail Expression ◽  
Gsk 3Β

scholarly journals TET2 regulates LncRNA-ANRIL expression and inhibits the growth of human gastric cancer cells

IUBMB Life ◽  
2016 ◽  
Vol 68 (5) ◽  
pp. 355-364 ◽  
Author(s):  
Wei Deng ◽  
Jin Wang ◽  
Jun Zhang ◽  
Jun Cai ◽  
Zhigang Bai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals Cre-loxP-mediated bax gene activation reduces growth rate and increases sensitivity to chemotherapeutic agents in human gastric cancer cells

2000 ◽  
Vol 7 (6) ◽  
pp. 885-892 ◽  
Author(s):  
Koga Komatsu ◽  
Susumu Suzuki ◽  
Tooru Shimosegawa ◽  
Jun-ichi Miyazaki ◽  
Takayoshi Toyota
Keyword(s):  
Gastric Cancer ◽  
Growth Rate ◽  
Cancer Cells ◽  
Gene Activation ◽  
Chemotherapeutic Agents ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Bax Gene

Identification of 14-3-3β in human gastric cancer cells and its potency as a diagnostic and prognostic biomarker

2011 ◽  
Vol 5 (9-10) ◽  
pp. 567-567
Author(s):  
Chien-Wei Tseng ◽  
Jyh-Chin Yang ◽  
Chiung-Nien Chen ◽  
Hsuan-Cheng Huang ◽  
Kai-Neng Chuang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Prognostic Biomarker ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

The Effect of Chloroquine on the Apoptosis Induced by Cisplatin in Human Gastric Cancer BGC823 Cells

2014 ◽  
Vol 926-930 ◽  
pp. 1124-1127
Author(s):  
Zhen Xun Jin ◽  
Li Li Zhang ◽  
Yan Wang ◽  
Lin Chuan Zeng ◽  
Yang Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Confocal Microscopy ◽  
Laser Scanning ◽  
Laser Scanning Confocal Microscopy ◽  
Combination Group ◽  
Human Gastric Cancer ◽  
Apoptotic Cells ◽  
Toxic Dose ◽  
Scanning Confocal Microscopy ◽  
Mtt Tests

The aim of this study is to investigate the effects and mechanism of chloroquine (CQ) on the apoptosis induced by cisplatin in human gastric cancer BGC823 cells. MTT assay was used to detect the state of cell growth. The appearances of cellular apoptosis were detected by laser scanning confocal microscopy and light microscopy. The expressions of LC3 and p62 were detected by laser scanning confocal microscopy. MTT tests showed that the non-toxic dose of CQ could increase the inhibition rate of BGC823 cells induced by cisplatin. Under the light microscope, the ratio of apoptotic cells in the group treated with non-toxic dose of CQ combined with cisplatin was higher than that in the group treated with cisplatin alone. Hoechst33342 staining showed that the ratio of apoptotic cells in the combination group was higher than that in the cisplatin group. The expression and colocalization of LC3 and p62 proteins were significantly increased in the combination group. These results indicate that CQ can enhance the cell apoptosis induced by cisplatin in BGC823 cells, which is through the inhibition of autophagy.

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