Dataset Information

A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia.

ABSTRACT: BACKGROUND Expression profiles of circular ribonucleic acids (circRNAs) have been recently reported in lung cancers including lung adenocarcinoma (LUAD). Hypoxia is a hallmark of lung cancers. However, the role of hsa_circ_0008193 (circ_0008193) in LUAD under hypoxia remains to be illuminated. MATERIAL AND METHODS Gene expression levels were detected using real-time quantitative polymerase chain reaction and western blotting. Cell proliferation, migration, invasion, and Warburg effect were detected using 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide assay, transwell assays, special kits, and xenograft experiments. The relationship among circ_0008193, micro (mi)RNA (miR)-1180-3p, and tripartite motif containing 62 (TRIM62) was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. RESULTS Expression of circ_0008193 was downregulated in human LUAD tumor tissues and cell lines (A549 and H1975), accompanied by miR-1180-3p upregulation and TRIM62 downregulation. Moreover, circ_0008193 downregulation was correlated with tumor size and lymph node metastasis. Functionally, circ_0008193 overexpression inhibited cell viability, glucose uptake, lactate production, migration, and invasion, as well as expression of hexokinase II, lactate dehydrogenase A, matrix metalloproteinase 2 (MMP2), and MMP9 in hypoxic LUAD cells in vitro. Furthermore, tumor growth of A549 cells in vivo was also hindered by circ_0008193 overexpression. Mechanically, circ_0008193 regulated TRIM62 expression via sponging miR-1180-3p, and TRIM62 was targeted by miR-1180-3p. Both miR-1180-3p upregulation and TRIM62 downregulation could abolish the suppressive role of circ_0008193 in LUAD cells. CONCLUSIONS Upregulating circ_0008193 inhibited LUAD cell proliferation, migration, invasion, and Warburg effect under hypoxia in vitro and in vivo through regulation of the miR-1180-3p/TRIM62 axis.

SUBMITTER: Chen M

PROVIDER: S-EPMC7444845 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia.

Chen Minbiao M Huang Xiuming X Li Liang L Huang Mingfang M Cai Renzhong R Liao Xuqiang X

Medical science monitor : international medical journal of experimental and clinical research 20200812

BACKGROUND Expression profiles of circular ribonucleic acids (circRNAs) have been recently reported in lung cancers including lung adenocarcinoma (LUAD). Hypoxia is a hallmark of lung cancers. However, the role of hsa_circ_0008193 (circ_0008193) in LUAD under hypoxia remains to be illuminated. MATERIAL AND METHODS Gene expression levels were detected using real-time quantitative polymerase chain reaction and western blotting. Cell proliferation, migration, invasion, and Warburg effect were detec ...[more]

PMID: 32782238

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Project description:ObjectiveIn the present study, we tried to describe the role of miR-29c-3p in esophageal carcinoma (EC) and the relationship of miR-29c-3p with CCNA2 as well as cell cycle, accordingly revealing the potential molecular mechanism across cell proliferation, migration and invasion.MethodsExpression profiles of EC miRNAs and matched clinical data were accessed from TCGA database for differential and survival analyses. Bioinformatics databases were employed to predict the downstream targets of the potential miRNA, and enrichment analysis was performed on the miRNA and corresponding target gene using GSEA software. qRT-PCR was conducted to detect the expression levels of miR-29c-3p and CCNA2 mRNA in EC tissues and cells, and Western blot was performed for the examination of CCNA2, CDK1 and p53 protein levels. Subsequently, cells were harvested for MTT, Transwell as well as flow cytometry assays to examine cell viability, migration, invasion and cell cycle. Dual-luciferase reporter gene assay and RIP were carried out to further investigate and verify the targeted relationship between miR-29c-3p and CCNA2.ResultsMiR-29c-3p was shown to be significantly down-regulated in EC tissues and able to predict poor prognosis. CCNA2 was found to be a downstream target of miR-29c-3p and mainly enriched in cell cycle and p53 signaling pathway, whereas miR-29c-3p was remarkably activated in cell cycle. MiR-29c-3p overexpression inhibited cell proliferation, migration and invasion, as well as arrested cells in G0/G1 phase. As suggested by dual-luciferase reporter gene assay and RIP, CCNA2 was under the regulation of miR-29c-3p, and the negative correlation between the two genes was verified. Silencing CCNA2 could suppress cell proliferation, migration and invasion, as well as activate p53 pathway, even was seen to reverse the inhibitory effect of PFTβ on p53. Besides, in the presence of low miR-29c-3p, CCNA2 was up-regulated while p53 was simultaneously inhibited, resulting in the promotion of cell migration, invasion and cell cycle arrest.ConclusionMiR-29c-3p plays a regulatory role in EC tumorigenesis and development. MiR-29c-3p can target CCNA2 to mediate p53 signaling pathway, finally attributing to the inhibition of cell proliferation, migration and invasion, and making cells arrest in G0/G1 phase.

Dataset Information

A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia.

Publications

A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia.

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