RETRACTED: Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2 Autoregulatory Loop in Multiple Myeloma Development (Retracted article. See vol. 40, pg. 1442, 2022)

被引：354

作者：

Pichiorri, Flavia ^{[1
,2
,3
,4
]}

Suh, Sung-Suk ^{[1
,2
,3
,4
]}

Rocci, Alberto ^{[5
]}

De Luca, Luciana ^{[6
]}

Taccioli, Cristian ^{[1
,2
,3
,7
]}

Santhanam, Ramasamy ^{[1
,2
,3
]}

Zhou, Wenchao ^{[8
]}

Benson, Don M., Jr. ^{[9
]}

Hofmainster, Craig ^{[9
]}

Alder, Hansjuerg ^{[1
,2
,3
]}

Garofalo, Michela ^{[1
,2
,3
]}

Di Leva, Gianpiero ^{[1
,2
,3
]}

Volinia, Stefano ^{[1
,2
,3
,10
]}

Lin, Huey-Jen ^{[8
]}

Perrotti, Danilo ^{[1
,2
,3
]}

Kuehl, Michael ^{[11
]}

Aqeilan, Rami I. ^{[1
,2
,3
,4
]}

Palumbo, Antonio ^{[5
]}

Croce, Carlo M. ^{[1
,2
,3
]}

机构：

[1] Ohio State Univ, Dept Mol Virol, Ctr Comprehens Canc, Columbus, OH 43210 USA

[2] Ohio State Univ, Dept Immunol, Ctr Comprehens Canc, Columbus, OH 43210 USA

[3] Ohio State Univ, Dept Human Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA

[4] Hebrew Univ Hadassah Med Sch, IMRIC Lautenberg Ctr Immunol & Canc Res, IL-91120 Jerusalem, Israel

[5] Univ Turin, Div Hematol, I-10149 Turin, Italy

[6] Referral Canc Ctr Basilicata Crob, IRCCS, Mol Oncol Unit, I-85028 Rionero In Vulture, PZ, Italy

[7] UCL, Inst Canc, London WC1E, England

[8] Ohio State Univ, Sch Allied Med Profess, Med Technol Div, Columbus, OH 43210 USA

[9] Ohio State Univ, Div Hematol & Oncol, Dept Med, Ctr Comprehens Canc, Columbus, OH 43210 USA

[10] Univ Ferrara, Telethon Facil Data Min Anal DNA Microarrays, Dept Morphol & Embryol, I-44100 Ferrara, Italy

[11] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20889 USA

来源：

CANCER CELL | 2010年 / 18卷 / 04期

关键词：

PHARMACOLOGICAL ACTIVATION; P53; PROLIFERATION; EXPRESSION; CANCER; RESTORATION; MIGRATION; MIR-192; ENHANCE; PATHWAY;

D O I：

10.1016/j.ccr.2010.09.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：367 / 381

页数：15

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