Dataset Information

Circ_0072088 Promotes Proliferation, Migration, and Invasion of Esophageal Squamous Cell Cancer by Absorbing miR-377.

ABSTRACT: Circular RNA (circRNA) is an endogenous noncoding RNA. Accumulative investigations have confirmed that circRNAs play a vital role in carcinogenesis and tumor progression. Herein, we examined the expression and mechanism of circ_0072088 in esophageal squamous cell carcinoma (ESCC). As a result, circ_0072088 was significantly overexpressed in ESCC tissues and cells, which was closely associated with tumor size, invasion depth, clinical stage, and lymph node metastasis of esophageal cancer. Nuclear and cytoplasmic separation as well as FISH assays showed that circ_0072088 was mainly localized in the cytoplasm of ESCC cells. RNase R treatment assay revealed that circ_0072088 was steadier than linear ZFR mRNA. circ_0072088 promoted ESCC cell proliferation, migration and invasion in vitro, and cell proliferation in vivo. Mechanistically, circ_0072088 upregulated VEGF gene expression by acting as the sponge of miRNA-377. In conclusion, circ_0072088 might be used as a diagnostic biomarker and therapeutic target for ESCC.

SUBMITTER: Fang N

PROVIDER: S-EPMC7542490 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circ_0072088 Promotes Proliferation, Migration, and Invasion of Esophageal Squamous Cell Cancer by Absorbing miR-377.

Fang Na N Shi Yijun Y Fan Yu Y Long Tao T Shu Yongqian Y Zhou Jianwei J

Journal of oncology 20200929

Circular RNA (circRNA) is an endogenous noncoding RNA. Accumulative investigations have confirmed that circRNAs play a vital role in carcinogenesis and tumor progression. Herein, we examined the expression and mechanism of circ_0072088 in esophageal squamous cell carcinoma (ESCC). As a result, circ_0072088 was significantly overexpressed in ESCC tissues and cells, which was closely associated with tumor size, invasion depth, clinical stage, and lymph node metastasis of esophageal cancer. Nuclear ...[more]

PMID: 33061973

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Project description:Despite investigations into microRNA (miRNA) expression in esophageal cancer (EC) tissue, miRNAs that participate in EC pathogenesis and their subsequent mechanisms of action remain to be determined. The present study aimed to identify important miRNAs that contribute to EC development, and to assess miRNA biomarkers that could be used in EC diagnosis, prognosis and therapy. Bioinformatics analysis was performed to reanalyze EC tissue miRNA expression microarray dataset GSE113776, which was followed by in vitro verification of miRNA functions using reverse transcription‑quantitative PCR, western blot analysis and a dual‑luciferase reporter assay. Out of 93 miRNAs extracted, only miR‑200a was significantly increased in EC tissues. Transfection of KYSE150 esophageal squamous cell carcinoma (ESCC) cells with miR‑200a mimics significantly increased their proliferative, migratory and invasive ability, whereas the opposite cell behaviors were observed in ESCC cells transfected with a miR‑200a inhibitor. A total of six miR‑200a target genes [catenin β1 (CTNNB1), cadherin‑1 (CDH1), PTEN, adenomatous polyposis coli (APC), catenin α1 (CTNNA1) and superoxide dismutase 2 (SOD2)] were selected for further analysis based on Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway analysis, protein‑protein interaction network map data and protein expression in esophageal tissue. These target genes were downregulated under miR‑200a expression and upregulated in the presence of the miR‑200a inhibitor. The association between miR‑200a and the 3'‑untranslated region of target genes in ESCC cells was confirmed using a dual‑luciferase reporter assay. In conclusion, the present study demonstrated that miR‑200a may participate in the promotion of ESCC cell proliferation, migration and invasion, and provided novel evidence for the direct interaction between miR‑200a and CTNNB1, CDH1, PTEN, APC, CTNNA1 and SOD2, which may contribute to the observed altered cell behavior.

Project description:PurposeMicroRNAs dysregulation has been confirmed in multiple malignancies. This paper reported the molecular mechanism of miR-204-5p in esophageal squamous cell carcinoma (ESCC).MethodsmiR-204-5p expression in 30 ESCC tumor tissues and 10 normal tissues was downloaded from RNA-seq data. ESCC tissues/normal tissues of 97 ESCC patients were collected. TE-1 and KYSE510 cells were transfected by miR-204-5p mimic, inhibitor, siYWHAZ or their corresponding controls. The phenotype of cells was detected by CCK-8 assay, transwell experiment, and flow cytometry. Luciferase reporter gene assay and RNA-binding protein immunoprecipitation (RIP) were performed to verify the targeting relationship between miR-204-5p and YWHAZ. miR-204-5p and YWHAZ expression in tissues/cells was detected by qRT-PCR and Western blot. Xenograft tumor experiment was performed.ResultsmiR-204-5p expression was declined in ESCC patients and cells, which was indicated the poor outcome of patients. Compared with siNC group, TE-1 cells in miR-204-5p inhibitor group had higher OD450 value, less cell percentage in G1 phase, and more cell percentage in S phase, lower apoptosis percentage, and higher migration and invasion cell numbers. Moreover, KYSE510 cells of miR-204-5p mimic group showed lower OD450 value, more cell percentage in G1 phase and less cell percentage in S phase, higher apoptosis percentage, and lower migration and invasion cell numbers than control. YWHAZ was directly inhibited by miR-204-5p. Relative to siNC group, TE-1 cells of miR-inhibitor group exhibited higher YWHAZ protein expression, higher OD450 value, less cell percentage in G1 phase and more cell percentage in S phase, lower apoptosis percentage, higher migration and invasion cell numbers, and higher p-PI3K/PI3K and p-AKT/AKT protein expression, while siYWHAZ rescued the effects of miR-inhibitor. miR-204-5p up-regulation inhibited ESCC growth in vivo.ConclusionmiR-204-5p inhibits ESCC progression by targeted inhibition of YWHAZ/PI3K/AKT.

Project description:The present study aimed to investigate the potential role of long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) in the progression of esophageal squamous cell carcinoma (ESCC) and to reveal its possible regulatory mechanism. The expression of lncRNA GAS5 in ESCC tissues and cell lines was analyzed using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The overexpression vector pc-GAS5 and control vector pc-negative control (NC), containing no GAS5 sequence, were transfected into ESCC cells. The effects of lncRNA GAS5 overexpression on cell proliferation, cell cycle distribution, cell migration and invasion were then analyzed. Besides, the expression levels of ATM-CHK2 pathway-associated proteins and epithelial-mesenchymal transition (EMT)-associated proteins were measured. Expression of lncRNA GAS5 was downregulated in the ESCC tissues compared with adjacent normal tissues, and was also downregulated in ESCC Kyse450 cells compared with the human esophageal epithelial HET-1A cell line. Additionally, lncRNA GAS5 was successfully overexpressed in ESCC cells following transfection with pc-GAS5. Overexpression of lncRNA GAS5 significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and suppressed cellular migration and invasion. When cells were transfected with pc-GAS5, the levels of phosphorylated (p)-ATM serine/threonine protein kinase, p-checkpoint kinase 2 (CHK2), p-cell division cycle 25C, p-cyclin-dependent kinase 1, N-cadherin, vimentin and Snail were significantly increased, whereas that of E-cadherin were markedly decreased. The results of the present study indicate that overexpression of lncRNA GAS5 may inhibit cell proliferation, migration and invasion in ESCC. lncRNA GAS5 overexpression may induce cell cycle arrest at G2/M stage by activating the ATM-CHK2 pathway. The results of the current study further indicate that lncRNA GAS5 overexpression may suppress cell migration and invasion via EMT-associated proteins. lncRNA GAS5 could therefore serve as a potential target for ESCC therapy.

Dataset Information

Circ_0072088 Promotes Proliferation, Migration, and Invasion of Esophageal Squamous Cell Cancer by Absorbing miR-377.

Publications

Circ_0072088 Promotes Proliferation, Migration, and Invasion of Esophageal Squamous Cell Cancer by Absorbing miR-377.

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