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.

Project description:Background:MicroRNA27b-3p (miR-27b) has been reported to be dysregulated in multiple types of human cancer. However, the expression levels, biological roles, and underlying mechanism of miR-27b in tongue squamous cell carcinoma (TSCC) remain to be elucidated. Methods:Bioinformatics analyses and quantitative real-time PCR (qRT-PCR) were used to determine miR-27b expression in TSCC tissues and cell lines. The influence of miR-27b overexpression or inhibition on TSCC cell proliferation, migration, and invasion in vitro, and on tumor growth in vivo, was explored via CCK8, colony formation, wound healing, and transwell assays, and in xenograft tumors in nude mice, respectively. Luciferase reporter assays, qRT-PCR, and Western blotting were performed to clarify the potential mechanisms involving miR-27b in TSCC cells. Results:miR-27b was significantly downregulated in TSCC tissues and cell lines, and its expression was correlated with cancer status. Overexpression of miR-27b led to diminished proliferation, migration, and invasion, and notably reduced tumor growth in vivo. Bioinformatics analysis followed by luciferase reporter assays demonstrated that miR-27b expression was inversely correlated with that of integrin subunit ?5 (ITGA5)and that miR-27b directly bound to the 3'-untranslated region of ITGA5 in TSCC cells. The bioinformatics analysis also indicated that ITGA5 was upregulated in TSCC and that its expression was correlated with epithelial-mesenchymal transition (EMT) and poor prognosis. Moreover, we found that miRNA-27b could reverse ITGA5-induced promotion of TSCC cell proliferation and migration. Finally, we demonstrated that regulation of miR-27b expression in TSCC may result in alterations in the expression of ITGA5 and EMT-related marker genes at the mRNA and protein levels. Conclusion:These results indicate that miR-27b hampers TSCC proliferation and migration via suppressing the EMT process by targeting ITGA5. These findings support consideration of miR-27b/ITGA5 as a valuable marker for the metastatic potential of TSCC, or as a therapeutic target for the treatment of TSCC.

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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