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miR-214 activates TP53 but suppresses the expression of RELA, CTNNB1, and STAT3 in human cervical and colorectal cancer cells
Published in John Wiley and Sons Ltd
2017
PMID: 29023799
Volume: 35
   
Issue: 7
Pages: 464 - 471
Abstract
High Mobility Group AT-hook 1 (HMGA1) was identified as a target of miR-214 in human cervical and colorectal cancers (CaCx and CRC) in a previous study. While the expression of miR-214 remains suppressed, HMGA1 behaves as a potent oncogene and plays crucial roles in several aberrant signalling pathways by interacting with intermediates like RELA, CTNNB1, STAT3, and TP53 in CaCx and CRC. Hypothetically, miR-214 should be able to regulate the stabilization of some of these intermediates through the regulation of HMGA1. This was assessed by ectopically expressing miR-214 or complementarily, by inhibiting the expression of HMGA1. In promoter luciferase assays, miR-214 inhibited NF-κB and Wnt activities but elevated TP53 activity in cancer cells. Further, miR-214 suppressed the expression of HMGA1, RELA, CTNNB1, and STAT3 while elevating TP53 levels, similar to when small interfering RNA (siRNA) against HMGA1 was used, as revealed by Western blotting. It is suggested that poor expression of miR-214, commonly reported in CaCx and CRC tissues, may not only result in the sustained expression of HMGA1 but also that of RELA, CTNNB1, and STAT3, and a congruent suppression of TP53 during cancer initiation/progression. These several states are, however, reversed when miR-214 is reintroduced and could explain the tumour suppressive functions observed in earlier studies. Further studies are, however, required to reveal how microRNA-mediated regulation of HMGA1 expression may affect individual signalling pathways in CaCx and CRC. Current results reveal that miR-214 is not only able to regulate the expression of its direct target, HMGA1, but also that of a few signalling intermediates like TP53, RELA, CTNNB1, and STAT3, with which HMGA1 interacts. These intermediates play crucial roles in signalling pathways commonly deregulated in human CaCx and CRC. Hence, it is proposed that miR-214 might act as a tumour suppressor by regulating several aberrant signalling pathways through HMGA1. This knowledge has the potential to help design novel therapeutic strategies in CaCx and CRC. Copyright © 2017 John Wiley & Sons, Ltd.
About the journal
JournalData powered by TypesetCell Biochemistry and Function
PublisherData powered by TypesetJohn Wiley and Sons Ltd
ISSN02636484
Open AccessNo
Concepts (61)
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    CTNNB1 PROTEIN
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    HIGH MOBILITY GROUP A PROTEIN
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    Immunoglobulin enhancer binding protein
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    MICRORNA 214
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    Protein
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    Protein p53
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    Small interfering rna
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    STAT3 PROTEIN
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    TRANSCRIPTION FACTOR RELA
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    Tumor necrosis factor
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    Unclassified drug
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    WNT PROTEIN
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    ANTAGOMIR
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    Beta catenin
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    CTNNB1 PROTEIN, HUMAN
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    HIGH MOBILITY GROUP A1A PROTEIN
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    Microrna
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    MIRN214 MICRORNA, HUMAN
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    RELA PROTEIN, HUMAN
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    STAT3 PROTEIN
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    TRANSCRIPTION FACTOR RELA
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    Article
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    Binding site
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    CELL ACTIVATION
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    Colorectal cancer
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    Controlled study
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    Down regulation
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    ECTOPIC EXPRESSION
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    Female
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    Gene repression
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    Gene targeting
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    Human
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    Human cell
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    Priority journal
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    Promoter region
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    Protein depletion
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    STABLE EXPRESSION
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    Upregulation
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    Uterine cervix cancer
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    WNT SIGNALING
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    Antagonists and inhibitors
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    COLORECTAL TUMOR
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    Genetics
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    Metabolism
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    Pathology
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    Rna interference
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    Tumor cell line
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    Uterine cervix tumor
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    ANTAGOMIRS
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    Cell line, tumor
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    COLORECTAL NEOPLASMS
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    Down-regulation
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    HMGA1A PROTEIN
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    Humans
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    Micrornas
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    Rna, small interfering
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    STAT3 TRANSCRIPTION FACTOR
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    TRANSCRIPTION FACTOR RELA
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    Tumor suppressor protein p53
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    Uterine cervical neoplasms
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    WNT SIGNALING PATHWAY