Dataset Information

DYNC1I1 Promotes the Proliferation and Migration of Gastric Cancer by Up-Regulating IL-6 Expression.

ABSTRACT: Gastric cancer is one of the top five malignant tumors worldwide. At present, the molecular mechanisms of gastric cancer progression are still not completely clear. Cytoplasmic dynein regulates intracellular transport and mitotic spindle localization, and its abnormal function is crucial for tumorigenesis, promotes tumor cell cycle progression, and tumor migration. DYNC1I1 is an important binding subunit of cytoplasmic dynein. However, studies on DYNC1I1 in tumors are currently limited. In the current study, we found that high DYNC1I1 expression in gastric cancer is associated with poor prognosis and is an independent prognostic factor. DYNC1I1 promoted the proliferation and migration of gastric cancer cells both in vitro and in vivo. DYNC1I1 also upregulated IL-6 expression by increasing NF-?B nuclear translocation. Collectively, these data revealed an important role for the DYNC1I1-driven IL-6/STAT pathway in gastric cancer proliferation and migration, suggesting that DYNC1I1 may be a potential therapeutic target for gastric cancer.

SUBMITTER: Gong LB

PROVIDER: S-EPMC6582752 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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DYNC1I1 Promotes the Proliferation and Migration of Gastric Cancer by Up-Regulating IL-6 Expression.

Gong Li-Bao LB Wen Ti T Li Zhi Z Xin Xing X Che Xiao-Fang XF Wang Jin J Liu Yun-Peng YP Qu Xiu-Juan XJ

Frontiers in oncology 20190612

Gastric cancer is one of the top five malignant tumors worldwide. At present, the molecular mechanisms of gastric cancer progression are still not completely clear. Cytoplasmic dynein regulates intracellular transport and mitotic spindle localization, and its abnormal function is crucial for tumorigenesis, promotes tumor cell cycle progression, and tumor migration. DYNC1I1 is an important binding subunit of cytoplasmic dynein. However, studies on DYNC1I1 in tumors are currently limited. In the c ...[more]

PMID: 31249807

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Project description:Objective:To explore the regulatory effects of circZNF609 on proliferative and migratory capacities of gastric cancer (GC) and its underlying mechanism. Methods:Expression level of circZNF609, CDK6 and miR-483-3p in GC tissues and cells were detected qRT-PCR verification. CCK-8 and transwell assay were conducted the cell viability and migratory capacities of GC cells. Dual luciferase assay was enrolled to confirm the interaction among circZNF609, CDK6 and miR-483-3p. Western blot was used to detect the protein level of CDK6. Results:Expression levels of circZNF609 were higher in GC patients by qRT-PCR.GC patients with higher expression of circZNF609 were expected to have a higher TNM stage and lower 5-year survival than those with lower expression. ROC curves showed a well diagnostic value of circZNF609 in GC. Treatment of RNase R in GC cells downregulated the expression of ZNF609, whereas circZNF609 expression did not change. Furthermore, cytoplasmic expression of circZNF609 was higher than those of nuclear expression. Besides, biological experiments indicated that overexpression of circZNF609 promoted the proliferative and migratory capacities of GC cells. To demonstrate the underlying mechanism of circZNF609, we found that circZNF609 bound to miR-483-3p, which presented a lower expression in GC tissues than that of paracancerous tissues. Both circZNF609 and miR-483-3p could bind to Ago2, suggesting that circZNF609 may act as a sponge of miR-483-3p. In addition, the effect of overexpressed circZNF609 on cellular behaviors of GC cells were partly reversed by overexpression of miR-483-3p. Bioinformatics suggested that CDK6 has a potential binding site with miR-483-3p. The expression of CDK6 markedly increased in GC tissues and cells, which was negatively correlated with miR-483-3p expression. Dual-luciferase reporter gene results indicated that miR-483-3p could bind to the 3'-UTR of CDK6. Moreover, miR-483-3p downregulated CDK6 at both mRNA and protein levels. Overexpression of miR-483-3p inhibited proliferative and migratory capacities of GC cells, which were reversed by CDK6 overexpression. Conclusion:In summary, the expression of circZNF609 is upregulated in GC. CircZNF609 can be used as the sponge of miR-483-3p to regulate the expression level of CDK6, thus participating in the progression of GC by regulating the proliferative and migratory capacities of GC cells.

Project description:BackgroundGlioma cells are characterized by high migration ability, resulting in aggressive growth of the tumors and poor prognosis of patients. It has been reported that the stress-induced hormone norepinephrine (NE) contributes to tumor progression through mediating a number of important biological processes in various cancers. However, the role of NE in the regulation of glioma migration is still unclear. Epithelial-to-mesenchymal transition (EMT) is one of the most important steps for tumor migration and metastasis. Twist1, as a key regulator of EMT, has been found to be elevated during glioma migration. But it is still unknown whether Twist1 is involved in the effect of NE on the migration of glioma cells.MethodsWound healing assay and transwell assay were conducted to evaluate the migration of glioma cells upon different treatments. The mesenchymal-like phenotype and the expression of Twist1 after NE treatment were assessed by cell diameters, real-time PCR, western blot and immunofluorescence staining. The gain-and loss-of-function experiments were carried out to investigate the biological function of Twist1 in the migration induced by NE. Finally, the clinical significance of Twist1 was explored among three public glioma datasets.ResultsIn this study, our finding revealed a facilitative effect of NE on glioma cell migration in a β-adrenergic receptor (ADRB)-dependent way. Mechanistically, NE induced mesenchymal-like phenotype and the expression of Twist1. Twist1 overexpression promoted glioma cells migration, while knockdown of Twist1 abolished the discrepancy in the migration ability between NE treated glioma cells and control cells. In addition, the clinical analysis demonstrated that Twist1 was up-regulated in malignant gliomas and recurrent gliomas, and predicted a poor prognosis of glioma patients.ConclusionsNE enhanced the migration ability of glioma cells through elevating the expression of Twist1. Our finding may provide potential therapeutic target for protecting patients with glioma from the detrimental effects of stress biology on the tumor progression.

Dataset Information

DYNC1I1 Promotes the Proliferation and Migration of Gastric Cancer by Up-Regulating IL-6 Expression.

Publications

DYNC1I1 Promotes the Proliferation and Migration of Gastric Cancer by Up-Regulating IL-6 Expression.

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