Dataset Information

CircSMAD2 inhibits the epithelial-mesenchymal transition by targeting miR-629 in hepatocellular carcinoma.

ABSTRACT: Background:Circular RNAs (circRNAs) are a class of widely distributed non-coding RNAs, which drew little attention for decades. Recent studies show that circRNAs are involved in cancer progression. Methods:The circSMAD2 expression in HCC and adjacent non-tumor tissues was measured by quantitative real-time polymerase chain reaction, and the biological function of circSMAD2 was explored by proliferation, apoptosis, migration, invasion, and Western blot assays. Next, the dual-luciferase reporter assay was performed to identify the target miRNA of circSMAD2. Finally, circSMAD2 and its target miRNA were co-transfected in HCC cells to investigate their relationship to HCC progression. Results:In this study, we found that circRNA SMAD2 (circSMAD2) expression was downregulated in hepatocellular carcinoma (HCC) tissues (P = 0.014) compared to the adjacent non-tumor tissues and markedly associated with the differentiation degree of the HCC tissues (P < 0.001). The in vitro experiments showed that overexpressed circSMAD2 inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) in HCC cells. Bioinformatics predicted that miR-629 is a potential target of circSMAD2, and the dual-luciferase reporter assay verified that miR-629 directly bound circSMAD2. In addition, we found that overexpression of circSMAD2 suppressed the expression of miR-629 in HCC cells, whereas knockdown of circSMAD2 upregulated the expression of miR-629. Furthermore, co-transfection of miR-629 mimics with circSMAD2 reversed the circSMAD2 effects of inhibiting the migration, invasion, and EMT of HCC cells. Conclusion:Altogether, our data support that circSMAD2 inhibits the migration, invasion, and EMT of HCC cells by targeting miR-629.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5962255 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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circSMAD2 inhibits the epithelial-mesenchymal transition by targeting miR-629 in hepatocellular carcinoma.

Zhang Xianwei X Luo Ping P Jing Wei W Zhou Hu H Liang Chunzi C Tu Jiancheng J

OncoTargets and therapy 20180516

<h4>Background</h4>Circular RNAs (circRNAs) are a class of widely distributed non-coding RNAs, which drew little attention for decades. Recent studies show that circRNAs are involved in cancer progression.<h4>Methods</h4>The circSMAD2 expression in HCC and adjacent non-tumor tissues was measured by quantitative real-time polymerase chain reaction, and the biological function of circSMAD2 was explored by proliferation, apoptosis, migration, invasion, and Western blot assays. Next, the dual-lucife ...[more]

PMID: 29844683

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Project description:Metastasis is responsible for the rapid recurrence and poor survival of malignancies. Epithelial-mesenchymal transition (EMT) has a critical role in metastasis. Increasing evidence indicates that EMT can be regulated by microRNAs (miRNAs). The aim of this study was to investigate the role of miR-26b in modulating epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC), as well as to identify its underlying mechanism of action.The expression level of miR-26b was assessed in multiple HCC cell lines (HepG2, MHCC97H, Hep3B, MHCC97L, HCCC9810, BEL-7402, Huh7 and QGY-7703), as well as in liver tissue from patients with HCC. Follow-up studies examined the effects of a miR-26b mimic (increased expression) and a miR-26b inhibitor (decreased expression) on markers of EMT, wound healing and cell migration. The molecular target of miR-26b was also identified using a computer algorithm and confirmed experimentally.MiR-26b expression was decreased in HCC cell lines and was inversely correlated with the grade of HCC. Increased expression of miR-26b inhibited the migration and invasiveness of HCC cell lines, which was accompanied by decreased expression of the epithelial marker E-cadherin and increased expression of the mesenchymal marker vimentin, at both the mRNA and protein expression levels. A binding site for miR-26b was theoretically identified in the 3'UTR of USP9X. Further studies revealed that overexpression of miR-26b repressed the endogenous level of USP9X protein expression. Overexpression of miR-26b also repressed Smad4 expression, whereas its inhibition elevated Smad4 expression.Taken together, our results indicate that miR-26b were inhibited in HCC. In HCC cell lines, miR-26b targeted the 3'UTR of USP9X, which in turn affects EMT through Smad4 and the TGF-? signaling pathway. Our analysis of clinical HCC samples verifies that miR-26b also targets USP9X expression to inhibit the EMT of hepatocytes. Thus, miR-26b may have some effects on the EMT of HCC cells.

Project description:BackgroundEpithelial-to-mesenchymal transition (EMT) is a key step of the progression of tumor cell metastasis. Recent work has demonstrated some miRNAs play critical roles in EMT. In this study, we focused on the roles of miR-300 in regulating EMT.MethodsThe expression levels of miR-300 were examined in epithelial carcinoma cells that underwent an EMT using quantitative reverse transcription-PCR. The role of miR-300 in EMT was investigated by transfection of the miR-300 mimic or inhibitor in natural epithelial-mesenchymal phenotype cell line pairs and in transforming growth factor (TGF) beta-induced EMT cell models. A luciferase reporter assay and a rescue experiment were conducted to confirm the target gene of miR-300. The efficacy of miR-300 against tumor invasion and metastasis was evaluated both in vitro and in vivo. Correlation analysis between miR-300 expression and the expression levels of its target gene, as well as tumor metastasis was performed in specimens from patients with head and neck squamous cell carcinoma (HNSCC).ResultsMiR-300 was found down-regulated in the HNSCC cells and breast cancer cells that underwent EMT. Ectopic expression of miR-300 effectively blocked TGF-beta-induced EMT and reversed the phenotype of EMT in HN-12 and MDA-MB-231 cells, but inhibition of miR-300 in the epithelial phenotype cells, HN-4 and MCF-7 cells, could induce EMT. The luciferase reporter assay and the rescue assay results showed that miR-300 directly targets the 3'UTR of Twist. Enforced miR-300 expression suppressed cell invasion in vitro and experimental metastasis in vivo. Clinically, miR-300 expression was found inversely correlated with Twist expression and reduced miR-300 was associated with metastasis in patient specimens.ConclusionsDown-regulation of miR-300 is required for EMT initiation and maintenance. MiR-300 may negatively regulate EMT by direct targeting Twist and therefore inhibit cancer cell invasion and metastasis, which implicates miR-300 as an attractive candidate for cancer therapy.

Dataset Information

CircSMAD2 inhibits the epithelial-mesenchymal transition by targeting miR-629 in hepatocellular carcinoma.

Publications

circSMAD2 inhibits the epithelial-mesenchymal transition by targeting miR-629 in hepatocellular carcinoma.

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