Abstract
Retinoblastoma (RB) is commonly-seen cancer in children. The p53 pathway dysfunction, which can lead to elevated MDM2 or MDM4 (p53 antagonists) protein expression, is frequently observed in almost all human cancers, including RB. The present study attempted to investigate the underlying mechanism from the perspective of non-coding RNA regulation. Here, we demonstrated that p53 and miR-129 were positively correlated with each other in RB. miR-129 directly targeted MDM2/4 to inhibit expression, therefore counteracting MDM2/4-mediated p53 signaling suppression and modulating RB cell proliferation and apoptosis. Moreover, p53 could activate the transcription of miR-129 via binding to the miR-129 promoter region, therefore forming a regulatory loop with MDM2/4 to affect RB progression. Altogether, the p53/miR-129/MDM2/4/p53 regulatory loop can modulate RB cell growth. We provide a solid experimental basis for developing novel therapies for RB.
Keywords:
MDM2/4; Retinoblastoma (RB); feedback loop; miR-129; p53.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / physiology
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Cell Proliferation / physiology
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Feedback, Physiological / physiology*
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HEK293 Cells
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Humans
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-mdm2 / genetics
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Proto-Oncogene Proteins c-mdm2 / metabolism*
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Retinoblastoma / genetics
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Retinoblastoma / metabolism*
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Retinoblastoma / prevention & control
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Cell Cycle Proteins
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MDM4 protein, human
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MicroRNAs
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Mirn129 microRNA, human
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Proto-Oncogene Proteins
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TP53 protein, human
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Tumor Suppressor Protein p53
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2
Grants and funding
Hunan Provincial Key Laboratory Construction Project for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine (2017TP1018) and National Administration of Traditional Chinese Medicine Key Discipline Construction Project of Ophthalmology of Traditional Chinese Medicine (ZK1801YK015).