Dataset Information

Circ_0003356 suppresses gastric cancer growth through targeting the miR-668-3p/SOCS3 axis.

ABSTRACT:

Background

Circular RNAs (circRNAs) have attracted extensive attention as therapeutic targets in gastric cancer (GC). Circ_0003356 is known to be downregulated in GC tissues, but its cellular function and mechanisms remain undefined.

Aim

To investigate the role of circ_0003356 in GC at the molecular and cellular level.

Methods

Circ_0003356, miR-668-3p, and SOCS3 expression were assessed via quantitative real time-polymerase chain reaction (qRT-PCR). Wound healing, EdU, CCK-8, flow cytometry and transwell assays were used to analyze the migration, proliferation, viability, apoptosis and invasion of GC cells. The subcellular localization of circ_0003356 was monitored using fluorescence in situ hybridization. The interaction of circ_0003356 with miR-668-3p was confirmed using RIP-qRT-PCR, RNA pull-down, and dual luciferase reporter assays. We observed protein levels of genes via western blot. We injected AGS cells into the upper back of mice and performed immunohistochemistry staining for examining E-cadherin, N-cadherin, Ki67, and SOCS3 expressions. TUNEL staining was performed for the assessment of apoptosis in mouse tumor tissues.

Results

Circ_0003356 and SOCS3 expression was downregulated in GC cells, whilst miR-668-3p was upregulated. Exogenous circ_0003356 expression and miR-668-3p silencing suppressed the migration, viability, proliferation, epithelial to mesenchy-mal transition (EMT) and invasion of GC cells and enhanced apoptosis. Circ_0003356 overexpression impaired tumor growth in xenograft mice. Targeting of miR-668-3p by circ_0003356 was confirmed through binding assays and SOCS3 was identified as a downstream target of miR-668-3p. The impacts of circ_0003356 on cell proliferation, apoptosis, migration, invasion and EMT were reversed by miR-668-3p up-regulation or SOCS3 down-regulation in GC cells.

Conclusion

Circ_0003356 impaired GC development through its interaction with the miR-668-3p/SOCS3 axis.

SUBMITTER: Li WD

PROVIDER: S-EPMC10237019 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circ_0003356 suppresses gastric cancer growth through targeting the miR-668-3p/SOCS3 axis.

Li Wei-Dong WD Wang Hai-Tao HT Huang Yue-Ming YM Cheng Bo-Hao BH Xiang Li-Jun LJ Zhou Xin-Hao XH Deng Qing-Yan QY Guo Zhi-Gang ZG Yang Zhi-Feng ZF Guan Zhi-Fen ZF Wang Yao Y

World journal of gastrointestinal oncology 20230501 5

<h4>Background</h4>Circular RNAs (circRNAs) have attracted extensive attention as therapeutic targets in gastric cancer (GC). Circ_0003356 is known to be downregulated in GC tissues, but its cellular function and mechanisms remain undefined.<h4>Aim</h4>To investigate the role of circ_0003356 in GC at the molecular and cellular level.<h4>Methods</h4>Circ_0003356, miR-668-3p, and SOCS3 expression were assessed <i>via</i> quantitative real time-polymerase chain reaction (qRT-PCR). Wound healing, Ed ...[more]

PMID: 37275445

Similar Datasets

Project description:BackgroundFasting mimic diet is an effect approach for gastric cancer (GC) treatment. Exploring mechanisms of glucose deprivation-mediated GC suppression is required to develop novel therapeutic regimens. Farnesyltransferase 1 (FDFT1), as a novel target in basic research, has been reported to regulate malignant progression in some types of cancer. However, biological functions of FDFT1 in GC are still unclear. This study focused on biological functions of FDFT1 in GC and the association between glucose starvation (GS) and FDFT1.MethodsThe data derived from the Kaplan-Meier Plotter database were collected to identify the relationship between survival time and FDFT1 expression levels of GC patients. Bioinformatic analysis was performed to explore the biological functions of FDFT1. The expression levels of targeted genes and microRNAs (miRNAs) were detected with immunohistochemistry, quantitative real-time PCR and western blot. Malignant behaviors were measured using cell counting, cell counting kit-8, 5-ethynyl-2-deoxyuridine, wound healing, invasion transwell assays in vitro and constructions of subcutaneous and lung-metastatic tumors in vivo. The glycolysis of GC cells was determined by a series of metabolites, including lactate acid, pyruvic acid, ATP production, rates of glucose uptake, extracellular acidification rate and oxygen consumption rate.ResultsFDFT1 was downregulated in GC and negatively correlated with pathological T stage, pathological TNM stage and cancer differentiation. High expression of FDFT1 also indicated better prognosis of GC patients. FDFT1 upregulation attenuated proliferation, migration and invasion of GC. miR-216a-5p was identified as a critical suppressor of FDFT1 expression and miR-216a-5p/FDFT1 axis regulated malignant behaviors and glycolysis of GC cells. GS suppressed malignant behaviors of GC by targeting miR-216a-5p/FDFT1 axis both in vitro and in vivo.ConclusionThis study illustrated novel mechanisms by which GS effectively suppresses GC. FDFT1 may become a potential prognostic indicator and novel target of GC therapy.

Dataset Information

Circ_0003356 suppresses gastric cancer growth through targeting the miR-668-3p/SOCS3 axis.

Background

Aim

Methods

Results

Conclusion

Publications

Circ_0003356 suppresses gastric cancer growth through targeting the miR-668-3p/SOCS3 axis.

Similar Datasets

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