Dataset Information

Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma.

ABSTRACT: Background:MIR155 host gene (MIR155HG) is a long noncoding RNA that has been considered as the primary micro (mi)RNA of miR-155. MIR155HG plays an essential role in hematopoiesis, inflammation, and tumorigenesis. Our study investigated the clinical significance, biological function, mechanisms, and small-molecule inhibitors of the MIR155HG/miR-155 axis in glioma. Methods:We analyzed the expression of the MIR155HG/miR-155 axis and the correlation with glioma grade and patient survival using 2 different glioma gene expression datasets. Biological significance was elucidated through a series of in vitro and in vivo experiments. Furthermore, we conducted a high-throughput screening for small molecules to identify a potential inhibitor of the MIR155HG/miR-155 axis. Results:Increased MIR155HG was associated with glioma grade, mesenchymal transition, and poor prognosis. Functionally, MIR155HG reduction by small interfering RNA inhibited cell proliferation, migration, invasion, and orthotopic glioma growth by repressing the generation of its derivatives miR-155-5p and miR-155-3p. Bioinformatics and luciferase reporter assays revealed that protocadherin 9 and protocadherin 7, which act as tumor suppressors by inhibiting the Wnt/?-catenin pathway, were direct targets of miR-155-5p and miR-155-3p, respectively. Finally, we identified NSC141562 as a potent small-molecule inhibitor of the MIR155HG/miR-155 axis. Conclusions:Our results demonstrate that the MIR155HG/miR-155 axis plays a critical role in facilitating glioma progression and serves as a prognostic factor for patient survival in glioblastoma. High-throughput screening indicated that the MIR155HG/miR-155 axis inhibitor NSC141562 may be a useful candidate anti-glioma drug.

SUBMITTER: Wu X

PROVIDER: S-EPMC5570208 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma.

Wu Xuechao X Wang Yingyi Y Yu Tianfu T Nie Er E Hu Qi Q Wu Weining W Zhi Tongle T Jiang Kuan K Wang Xiefeng X Lu Xiaojie X Li Hailin H Liu Ning N Zhang Junxia J You Yongping Y

Neuro-oncology 20170901 9

<h4>Background</h4>MIR155 host gene (MIR155HG) is a long noncoding RNA that has been considered as the primary micro (mi)RNA of miR-155. MIR155HG plays an essential role in hematopoiesis, inflammation, and tumorigenesis. Our study investigated the clinical significance, biological function, mechanisms, and small-molecule inhibitors of the MIR155HG/miR-155 axis in glioma.<h4>Methods</h4>We analyzed the expression of the MIR155HG/miR-155 axis and the correlation with glioma grade and patient survi ...[more]

PMID: 28371892

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Project description:BackgroundGlioma metastasis, invasion, epithelial-mesenchymal transition (EMT) and chemoresistance indicate poor prognosis. Accumulating evidence reveals that Notch1 is an important factor in tumour progression. However, the role of Notch1 in glioma EMT and associated microRNAs (miRNAs) with the Notch pathway remain controversial.MethodsUtilizing cBioPortal database to examine the gene signature of NOTCH1 (encoding Notch1), CDH2 (encoding N-cadherin) and SNAI1 (encoding Snail-1) in disease-free survival (DFS) and overall survival (OS). We analyzed the Notch1 expression from Oncomine. We used Western blot (WB), immunohistochemistry (IHC) and immunofluorescence to determine protein levels. Transcription was evaluated by quantitative real-time (qRT)-PCR. siRNA and lentivirus were used to knock down Notch1 and overexpress miR-139-5p, respectively. The migration and invasion of glioma cells were assessed by wound healing and transwell assays. Luciferase reporter assays were utilized to verify the relationship between Notch1 and miR-139-5p. A U87-implanted intracranial model was used to study the effect of miR-139-5p on tumour growth and Notch1 suppression efficacy or EMT reversion.ResultsIt revealed the association of NOTCH1, CDH2, SNAI1 genomic alterations with decreases in DFS and OS. Notch1 was upregulated in classical and proneural subtypes of GBM, and associated with tumour grade. Notch1 inhibition suppressed the biological behaviours of metastasis, invasion and EMT. Notch1 was identified as a novel direct target of miR-139-5p. MiR-139-5p overexpression partially phenocopied Notch1 siRNA, whereas the forced expression of Notch1 reversed the effects of miR-139-5p on the invasion of glioma. Moreover, intracranial tumourigenicity and EMT behaviours were reduced by the introduction of miR-139-5p and partially mediated by the decreased Notch1 expression.ConclusionsmiR-139-5p was identified as a tumour suppressor by negatively targeting Notch1, and this work suggests a possible molecular mechanism of the miR-139/Notch1/EMT axis for glioma treatment.

Project description:Non‑coding RNAs, particularly long non‑coding RNAs (lncRNAs), play important roles in tumorigenesis. The miR‑155 host gene (MIR155HG) lncRNA has been found to play a crucial role in tumor progression. However, the role of MIR155HG in laryngeal squamous cell carcinoma (LSCC) remains unclear. Thus, the aim of the present study was to explore the roles and underlying molecular mechanisms of action of MIR155HG and miR‑155‑5p in LSCC, in an effort to provide novel approaches for the antitumor therapy for LSCC. In the present study, the expression levels of miR‑155‑5p and MIR155HG were detected by reverse tran-scription‑quantitative polymerase chain reaction. In addition, the biological functions of MIR155HG and miR‑155‑5p on LSCC were evaluated in vitro by MTS assay, colony formation assay and Transwell assays, and in vivo by tumorigenesis assays. It was revealed that MIR155HG and miR‑155‑5p were significantly upregulated in LSCC tissues, and were associated with the TNM stage, pathological differentiation and lymph node metastasis. Moreover, the knockdown of MIR155HG and miR‑155‑5p inhibited the proliferation, migration and invasion of LSCC cells, whereas their overexpression exerted the opposite effects in vitro and MIR155HG overexpression promoted tumorigenesis in vivo. Furthermore, MIR155HG downregulation reduced the expression level of miR‑155‑5p. The inhibitory effect of MIR155HG knockdown on malignant behavior was abrogated by miR‑155‑5p overexpression. Bioinformatics analysis and luciferase reporter assay confirmed that miR‑155‑5p contributed to the progression of LSCC by directly binding to the 3' untranslated region of SRY‑related‑HMG‑box 10 (SOX10). In addition, MIR155HG and miR‑155‑5p were upregulated by the induction of transforming growth factor‑β (TGF‑β) and promoted the expression of mesenchymal markers synergistically. On the whole, the findings of the present study indicate a novel role of MIR155HG in the TGF‑β‑induced EMT of LSCC cells by regulating EMT markers through the miR‑155/SOX10 axis. The MIR155HG/miR‑155‑5p/SOX10 axis plays an important role in promoting the progression of LSCC and may thus serve as a potential therapeutic target for LSCC treatment.

Project description:Purpose: Circular RNAs (circRNAs) have been reported to regulate the incidence of tumor by regulating the transcriptional level and post-transcriptional level of tumor-related genes, and are significantly correlated with tumor metastasis and progression. CircRNA_100395 (circ_100395) has been reported to suppress lung cancer cell proliferation, and might act as an oncogene in deveopment of various cancers. However, the expression and function of circ_100395 in ovarian cancer has not been systematically researched. Methods: The expression of circ_100395 in ovarian cancer tissues was detected by Real-time Quantitative polymerase chain reaction (RT-qPCR), while the relationship between circ_100395 expression and clinicopathological characteristics was further analyzed. After increasing the expression of circ_100395 by plasmid transfection in ovarian cancer cells, we further investigated the cell proliferation, invasion and migration by cell counting kit-8 (CCK-8), and Transwell assays. Epithelial-mesenchymal transition (EMT) pathway was also measured by western blotting. In addition, the relationship among circ_100395, miR-1228 and p53 in ovarian cancer, was explored by luciferase reporter assay. Results: The expression of circ_100395 was found to be significantly down-regulated in ovarian cancer, while low expression of circ_100395 was highly correlated with the poor outcomes. In addition, upregulation of circ_100395 could significantly inhibit tumor growth, metastasis and EMT signaling pathway in ovarian cancer. Furthermore, the expression level of circ_100395 was negatively correlated with the expression of miR-1228, and with the addition of miR-1228 could reverse anti-cell proliferation effect induced by circ_100395 in ovarian cancer cells. In addition, p53 might be the key target of circ_100395 / miR-1228 axis in ovarian cancer. Conclusion: CircRNA_100395 could inhibit cell growth and metastasis of ovarian cancer cells via regulating the miR-1228/p53/EMT axis.

Dataset Information

Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma.

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Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma.

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