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 ◽  
...  

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.

2020 ◽  
Author(s):  
Jinshan Liu ◽  
Ximing Huang ◽  
Liran Wu ◽  
Zhiqiang Zhao ◽  
Kun Fan

Abstract Objective: MiR-498 has emerged as a potential molecular target for several cancer. In this study, we aimed to investigate the important function and mechanisms of miR-498 in gastric cancer.Methods: To detect the important roles of miR-498 in gastric cancer, we first measured its expression by RT-qPCR in gastric cancer cell lines. The impact of the miR-498 on gastric cancer cell proliferation were detected by CCK-8 and colony formation assays. The effect of the miR-498 on the cell apoptosis and cell cycle were detected by flow cytometry. We also used the scratch and transwell chamber assays to measure the cell migration and invasion. The expression levels of related proteins were assessed by western blot. The bioinformatics analysis was used to explore the target gene of miR-498. RT-qPCR and western blot assays were used to detect the expression levels of FOXK1 in response to miR-498 overexpression. In order to prove the role of FOXK1 in mediating the effect of miR-498 on the gastric cancer, CCK-8, colony formation, transwell chamber and flow cytometry assays were used for the further investigations.Results: The expression level of miR-498 is downregulated in gastric cancer cell lines. Overexpression of miR-498 inhibited proliferation and migration/invasion, while promoted the apoptosis of gastric cancer cells. Bioinformatics analysis indicated that miR-498 targeted on FOXK1 to inhibit the gastric cancer in vitro.Conclusion: MiR-498/FOXK1 axis may be a potential therapeutic target for the treatment of gastric cancers.


2021 ◽  
Vol 14 (3) ◽  
pp. 230
Author(s):  
Waseem El-Huneidi ◽  
Khuloud Bajbouj ◽  
Jibran Sualeh Muhammad ◽  
Arya Vinod ◽  
Jasmin Shafarin ◽  
...  

Gastric cancer is among the most common malignancies worldwide. Due to limited availability of therapeutic options, there is a constant need to find new therapies that could target advanced, recurrent, and metastatic gastric cancer. Carnosic acid is a naturally occurring polyphenolic abietane diterpene derived from Rosmarinus officinalis and reported to have numerous pharmacological effects. In this study, the cytotoxicity assay, Annexin V-FITC/PI, caspases 3, 8, and 9, cell cycle analysis, and Western blotting were used to assess the effect of carnosic acid on the growth and survival of human gastric cancer cell lines (AGS and MKN-45). Our findings showed that carnosic acid inhibited human gastric cancer cell proliferation and survival in a dose-dependent manner. Additionally, carnosic acid is found to inhibit the phosphorylation/activation of Akt and mTOR. Moreover, carnosic acid enhanced the cleavage of PARP and downregulated survivin expression, both being known markers of apoptosis. In conclusion, carnosic acid exhibits antitumor activity against human gastric cancer cells via modulating the Akt-mTOR signaling pathway that plays a crucial role in gastric cancer cell proliferation and survival.


2009 ◽  
Vol 155 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Hideyo Miyato ◽  
Joji Kitayama ◽  
Hiroharu Yamashita ◽  
Daisuke Souma ◽  
Masahiro Asakage ◽  
...  

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