Dataset Information

Overexpression of suppressive microRNAs, miR-30a and miR-200c are associated with improved survival of breast cancer patients.

ABSTRACT: Some microRNAs (miRNAs) are known to suppress breast cancer. However, whether the expressions of these tumor suppressive miRNAs translate to patient survival were not investigated in large cohort. Nine miRNAs (miR-30a, miR-30c, miR-31, miR-126, miR-140, miR-146b, miR-200c, miR-206, and miR-335) known to be tumor suppressive miRNAs in breast cancer were investigated in Genomic Data Common data portal miRNA-Seq dataset and The Cancer Genome Atlas (TCGA) (n?=?1052). Of the 9 miRNAs, miR-30a, miR-30c, miR-126, miR-140, miR-206, and miR-335 were found to have significantly lower expression in breast cancer tissues compared to paired normal breast tissue. High expression of miR-30a or miR-200c was associated with significantly better overall survival (OS). Gene Set Enrichment Analysis (GSEA) demonstrated that low expression levels of miR-30a had the tendency to associate with gene enrichment of EMT, while miR-200c did not, in TCGA cohort, and our findings support the need of validation using large cohort to use miRNA as prognostic biomarker for patients with breast cancer.

SUBMITTER: Kawaguchi T

PROVIDER: S-EPMC5698306 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Overexpression of suppressive microRNAs, miR-30a and miR-200c are associated with improved survival of breast cancer patients.

Kawaguchi Tsutomu T Yan Li L Qi Qianya Q Peng Xuan X Gabriel Emmanuel M EM Young Jessica J Liu Song S Takabe Kazuaki K

Scientific reports 20171121 1

Some microRNAs (miRNAs) are known to suppress breast cancer. However, whether the expressions of these tumor suppressive miRNAs translate to patient survival were not investigated in large cohort. Nine miRNAs (miR-30a, miR-30c, miR-31, miR-126, miR-140, miR-146b, miR-200c, miR-206, and miR-335) known to be tumor suppressive miRNAs in breast cancer were investigated in Genomic Data Common data portal miRNA-Seq dataset and The Cancer Genome Atlas (TCGA) (n = 1052). Of the 9 miRNAs, miR-30a, miR-30 ...[more]

PMID: 29162923

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Project description:BackgroundAberrant expression of Wiskott-Aldrich syndrome protein interacting protein family member 1 (WIPF1) contributes to the invasion and metastasis of several malignancies. However, the role of WIPF1 in human pancreatic ductal adenocarcinoma (PDAC) remains poorly understood.MethodsHuman pancreatic cancer samples from PDAC patients were collected for methylation analysis. Bioinformatic prediction program and luciferase reporter assay were used to identify microRNAs regulating WIPF1 expression. The association between WIPF1 expression and the overall survival (OS) of patients with PDAC was evaluated by using The Cancer Genome Atlas (TCGA) database. The roles of miR-141/200c and WIPF1 on the invasion and metastasis of PDAC cells were investigated both in vitro and in vivo.ResultsWe found that compared to the surrounding non-cancerous tissues, there was significantly increased methylation of miR-200c and miR-141 in human PDAC tissues that resulted in their silencing, whereas the members of the other cluster of miR-200 family including miR-200a, miR-200b and miR-429 were hypomethylated. Our data show that forced expression of miR-141 or miR-200c suppressed invasion and metastasis of PDAC cells both in vitro and in xenograft and identified WIPF1 as a direct target of miR-141 and miR-200c. Both miR-141 and miR-200c inhibit WIPF1 by directly interacting with its 3'-untranslated region. Remarkably, silencing of WIPF1 blocked PDAC growth and metastasis both in vitro and in vivo, whereas forced WIPF1 overexpression antagonized the tumor suppressive effect of miR-141/200c. Additionally, by using TCGA database we showed that high expression of WIPF1 correlated with poor survival in patients with PDAC. Moreover, we show that miR-141 and miR-200c blocked YAP/TAZ expression by suppressing WIPF1.ConclusionsWe have identified WIPF1 as an oncoprotein in PDAC and a direct target of miR-141/miR-200c. We have also defined the miR-141/200c-WIPF1-YAP/TAZ as a novel signaling pathway that is involved in the regulation of the invasion and metastasis of human PDAC cells.

Dataset Information

Overexpression of suppressive microRNAs, miR-30a and miR-200c are associated with improved survival of breast cancer patients.

Publications

Overexpression of suppressive microRNAs, miR-30a and miR-200c are associated with improved survival of breast cancer patients.

Similar Datasets

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