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Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development.

ABSTRACT: In multiple myeloma (MM), an incurable B cell neoplasm, mutation or deletion of p53 is rarely detected at diagnosis. Using small-molecule inhibitors of MDM2, we provide evidence that miR-192, 194, and 215, which are downregulated in a subset of newly diagnosed MMs, can be transcriptionally activated by p53 and then modulate MDM2 expression. Furthermore, ectopic re-expression of these miRNAs in MM cells increases the therapeutic action of MDM2 inhibitors in vitro and in vivo by enhancing their p53-activating effects. In addition, miR-192 and 215 target the IGF pathway, preventing enhanced migration of plasma cells into bone marrow. The results suggest that these miRNAs are positive regulators of p53 and that their downregulation plays a key role in MM development.

SUBMITTER: Pichiorri F

PROVIDER: S-EPMC3561766 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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RETRACTED: Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development.

Pichiorri Flavia F Suh Sung-Suk SS Rocci Alberto A De Luca Luciana L Taccioli Cristian C Santhanam Ramasamy R Zhou Wenchao W Benson Don M DM Hofmainster Craig C Alder Hansjuerg H Garofalo Michela M Di Leva Gianpiero G Volinia Stefano S Lin Huey-Jen HJ Perrotti Danilo D Kuehl Michael M Aqeilan Rami I RI Palumbo Antonio A Croce Carlo M CM

Cancer cell 20101001 4

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the editors. This article was published on October 19, 2010, and Figures 4A and 7A were later corrected on August 8, 2016. In January 2021, The Ohio State University notified the Cancer Cell editors that an internal investigation concluded that Figures 1E, 4A, 4D, 5A, and 7A were falsified and that part of Figure 1 ...[more]

PMID: 20951946

Dataset Information

Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development.

Publications

RETRACTED: Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development.

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