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microRNA-145 modulates epithelial-mesenchymal transition and suppresses proliferation, migration and invasion by targeting SIP1 in human cervical cancer cells
Published in Springer Netherlands
2017
PMID: 27933466
Volume: 40
   
Issue: 2
Pages: 119 - 131
Abstract
Purpose: Previously, it has been reported that microRNA-145 (miR-145) is lowly expressed in human cervical cancers and that its putative tumour suppressive role may be attributed to epithelial-mesenchymal transition (EMT) regulation. Here, we aimed to assess whether miR-145 may affect EMT-associated markers/genes and suppress cervical cancer growth and motility, and to provide a mechanistic basis for these phenomena. Methods: The identification of the SMAD-interacting protein 1 (SIP1) mRNA as putative miR-145 target was investigated using a 3’ untranslated region (3’UTR) luciferase assay and Western blotting, respectively. The functional effects of exogenous miR-145 expression, miR-145 suppression or siRNA-mediated SIP1 expression down-regulation in cervical cancer-derived C33A and SiHa cells were analysed using Western blotting, BrdU incorporation (proliferation), transwell migration and invasion assays. In addition, the expression levels of miR-145 and SIP1 were determined in primary human cervical cancer and non-cancer tissue samples using qRT-PCR. Results: We found that miR-145 binds to the wild-type 3’UTR of SIP1, but not to its mutant counterpart, and that, through this binding, miR-145 can effectively down-regulate SIP1 expression. In addition, we found that exogenous miR-145 expression or siRNA-mediated down-regulation of SIP1 expression attenuates the proliferation, migration and invasion of C33A and SiHa cells and alters the expression of the EMT-associated markers CDH1, VIM and SNAI1, whereas inhibition of endogenous miR-145 expression elicited the opposite effects. The expression of miR-145 in cervical cancer tissue samples was found to be low, while that of SIP1 was found to be high compared to non-cancerous cervical tissues. An inverse expression correlation between the two was substantiated through the anlaysis of data deposited in the TCGA database. Conclusion: Our data indicate that low miR-145 expression levels in conjunction with elevated SIP1 expression levels may contribute to cervical cancer development. MiR-145-mediated regulation of SIP1 provides a novel mechanistic basis for its tumour suppressive mode of action in human cervical cancer cells. © 2016, International Society for Cellular Oncology.
About the journal
JournalData powered by TypesetCellular Oncology
PublisherData powered by TypesetSpringer Netherlands
ISSN22113428
Open AccessNo
Concepts (67)
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    BROXURIDINE
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    Messenger rna
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    MICRORNA 145
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    SMAD PROTEIN
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    SMAD PROTEIN 1
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    Small interfering rna
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    Tumor marker
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    Unclassified drug
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    UVOMORULIN
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    VIMENTIN
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    Zinc finger protein
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    GEMIN2 PROTEIN, HUMAN
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    Microrna
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    MIRN145 MICRORNA, HUMAN
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    NERVE PROTEIN
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    RNA BINDING PROTEIN
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    3' UNTRANSLATED REGION
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    Article
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    BRDU ASSAY
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    CANCER GROWTH
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    Cancer inhibition
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    CARCINOGENESIS
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    Cell invasion
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    CELL INVASION ASSAY
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    Cell migration
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    CELL MIGRATION ASSAY
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    Cell motility
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    Cell proliferation
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    CERVICAL CANCER CELL LINE
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    Clinical article
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    Controlled study
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    Down regulation
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    ECTOPIC EXPRESSION
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    Epithelial mesenchymal transition
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    Female
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    Human
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    Human cell
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    Human tissue
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    LUCIFERASE ASSAY
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    PRIMARY TUMOR
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    Priority journal
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    Protein targeting
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    Uterine cervix cancer
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    Western blotting
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    Cell motion
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    Gene expression regulation
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    Gene silencing
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    Genetics
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    Metabolism
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    Nucleotide sequence
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    Pathology
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    Tumor cell line
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    Tumor invasion
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    Uterine cervix tumor
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    Base sequence
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    BIOMARKERS, TUMOR
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    Cell line, tumor
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    Cell movement
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    Epithelial-mesenchymal transition
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    GENE EXPRESSION REGULATION, NEOPLASTIC
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    GENE KNOCKDOWN TECHNIQUES
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    Humans
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    Micrornas
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    Neoplasm invasiveness
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    NERVE TISSUE PROTEINS
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    RNA-BINDING PROTEINS
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    Uterine cervical neoplasms