Fluorouracil induces autophagy-related gastric carcinoma cell death through Beclin-1 upregulation by miR-30 suppression

Yang, Ching-Ching; Pan, Yong

doi:10.1007/s13277-015-3775-6

Cited by 32 publications

(26 citation statements)

References 33 publications

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“…Induction of autophagy can either be a pro-survival mechanism protecting cells against stress-induced killing [45,46] or a cell death mechanism induced by various anti-cancer agents [43,44,[47][48][49][50]. Our results showed that cells with initiation of autophagy were more resistant to Tenovin-6, although the autophagy flux was blocked (Figure 3), suggesting a protective role of autophagy in these cells.…”

Section: Discussionmentioning

confidence: 67%

Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine

Qin

Deng

et al. 2020

Cancers

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Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer death. Approximately 15% of GC is associated with Epstein–Barr virus (EBV). GC is largely incurable with a dismal five-year survival rate. There is an urgent need to identify new therapeutic agents for the treatment of GC. Tenovin-6 was initially identified as a p53 activator, but it was later found to inhibit autophagy flux, and the protein deacetylase activity of sirtuins. Tenovin-6 shows promising therapeutic effect in various malignancies. However, it remains unknown whether Tenovin-6 is effective for GC. In this study, we found that EBV-positive and -negative GC cell lines were sensitive to Tenovin-6 but with different response times and doses. Tenovin-6 suppressed anchorage-independent growth of GC cells. Tenovin-6 induced different levels of apoptosis and phases of cell-cycle arrest depending on the cell lines with some manifesting gap 1 (G1) and others showing synthesis (S) phase cell-cycle arrest. Mechanistically, Tenovin-6 induced autophagy or p53 activation in GC cells depending on the status of TP53 gene. However, initiation of autophagy following treatment with Tenovin-6 conferred some protective effect on numerous cells. Combined treatment with Tenovin-6 and autophagy inhibitor chloroquine increased the cytotoxic effect by inducing microtubule-associated protein 1 light chain 3B (LC3B)-II accumulation, and by enhancing apoptosis and cell-cycle arrest. These results indicated that Tenovin-6 can be used as a potential therapeutic agent for GC, but the genetic background of the cancer cells might determine the response and mechanism of action. Treatment with Tenovin-6 alone or in combination with chloroquine could be a promising therapeutic approach for GC.

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Section: Discussionmentioning

confidence: 67%

Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine

Qin

Deng

et al. 2020

Cancers

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“…Aberrant or excessive autophagic activity may produce cytotoxicity, resulting in autophagic cell death and suppressing tumor development in GC cells (Qian and Yang, 2016). Fluorouracil (5-FU) may induce cell proliferation arrest and autophagic cell death in GC cells by suppressing miR-30, resulting in upregulating Beclin1 (Yang and Pan, 2015). On the other hand, autophagy promotes tumor progression and prevents cancer cells from undergoing drug-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

ERas Enhances Resistance to Cisplatin-Induced Apoptosis by Suppressing Autophagy in Gastric Cancer Cell

Tian

Wang

Meng

et al. 2020

Front. Cell Dev. Biol.

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Gastric cancer (GC), a common type of malignant cancer, remains the fifth most frequently diagnosed cancer and the third leading cause of cancer-related deaths worldwide. Despite developments in the treatment of GC, the prognosis remains poor. Embryonic stem cell-expressed Ras (ERas), a novel member of the Ras protein family, has recently been identified as an oncogene involved in the tumorigenic growth of embryonic stem cells. A recent study reported that ERas is expressed in most GC cell lines and GC specimens, and it promotes tumorigenicity in GC through induction of the epithelial mesenchymal transition (EMT) and activation of the PI3K/AKT pathway. Here, we found that ERas blocked autophagy flux in BGC-823 and AGS GC cells, which may occur through activation of the AKT/mTOR signaling pathway. Moreover, ERas overexpression suppressed cisplatin-induced apoptosis, and rapamycin treatment significantly attenuated ERas-mediated cisplatin resistance in GC cells. These data suggest that ERas may be a potential therapeutic target to improve the outcomes of GC patients by regulating the autophagy process.

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“…Conversely, high-level of autophagy was also demonstrated to suppress GC in other studies [9,12]. Some studies have given evidence that the upregulated autophagy can play a tumor suppressor role in GC cells [9,13]. For instance, Yang et al found that 5-Fu can suppress GC cells via inducing autophagy [13].…”

Section: Introductionmentioning

confidence: 94%

“…Some studies have given evidence that the upregulated autophagy can play a tumor suppressor role in GC cells [9,13]. For instance, Yang et al found that 5-Fu can suppress GC cells via inducing autophagy [13]. In addition, other pharmacological treatments can induce the autophagic cell death in GC cells [14,15].…”

Section: Introductionmentioning

confidence: 99%

Development of a Survival Model Based on Autophagy-Associated Genes for Predicting Prognosis of Gastric Cancer

Yang¹,

Duan²,

Zhao³

et al. 2020

Preprint

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Background: Gastric cancer (GC) is one of lethal diseases worldwide. Autophagy-associated genes play a crucial role in the cellular processes of GC. Our study aimed to investigate and identify the prognostic potential of autophagy-associated genes signature in GC. Methods: RNA-seq and clinical information of GC and normal controls were downloaded from The Cancer Genome Atlas (TCGA) database. Then, the Wilcoxon signed-rank test was used to pick out the differentially expressed autophagy-associated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential roles and mechanisms of autophagy-associated genes in GC. Cox proportional hazard regression analysis and Lasso regression analysis were carried out to identify the overall survival (OS) related autophagy-associated genes, which were then collected to construct a predictive model. Kaplan-Meier method and receiver operating characteristic (ROC) curve were utilized to validate the accuracy of this model. Finally, a clinical nomogram was established by combining the clinical factors and autophagy-associated genes signature. Results: A total of 28 differentially expressed autophagy-associated genes were identified. GO and KEGG analyses revealed that several important cellular processes and signaling pathways were correlated with these genes. Through Cox regression and Lasso regression analyses, we identified 4 OS-related autophagy-associated genes (GRID2, ATG4D, GABARAPL2, and CXCR4) and constructed a prognosis prediction model. GC Patients with high-risk had a worse OS than those in low-risk group (5-year OS, 27.7% vs 38.3%; P=9.524e-07). The area under the ROC curve (AUC) of the prediction model was 0.67. The nomogram was demonstrated to perform better for predicting 3-year and 5-year survival possibility for GC patients with a concordance index (C-index) of 0.70 (95% CI: 0.65-0.72). The calibration curves also presented good concordance between nomogram-predicted survival and actual survival. Conclusions: We constructed and evaluated a survival model based on the autophagy-associated genes for GC patients, which may improve the prognosis prediction in GC.

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Fluorouracil induces autophagy-related gastric carcinoma cell death through Beclin-1 upregulation by miR-30 suppression

Cited by 32 publications

References 33 publications

Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine

Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine

ERas Enhances Resistance to Cisplatin-Induced Apoptosis by Suppressing Autophagy in Gastric Cancer Cell

Development of a Survival Model Based on Autophagy-Associated Genes for Predicting Prognosis of Gastric Cancer

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