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Copy number gain of hsa-miR-569 at 3q26.2 leads to loss of TP53INP1 and aggressiveness of epithelial cancers. Cancer Cell 2014 Dec 08;26(6):863-879

Date

12/10/2014

Pubmed ID

25490449

Pubmed Central ID

PMC4261159

DOI

10.1016/j.ccell.2014.10.010

Scopus ID

2-s2.0-84919477596   31 Citations

Abstract

Small noncoding miRNAs represent underexplored targets of genomic aberrations and emerging therapeutic targets. The 3q26.2 amplicon is among the most frequent genomic aberrations in multiple cancer lineages including ovarian and breast cancers. We demonstrate that hsa-miR-569 (hereafter designated as miR569), which is overexpressed in a subset of ovarian and breast cancers, at least in part due to the 3q26.2 amplicon, alters cell survival and proliferation. Downregulation of TP53INP1 expression by miR569 is required for the effects of miR569 on survival and proliferation. Targeting miR569 sensitizes ovarian and breast cancer cells overexpressing miR569 to cisplatin by increasing cell death both in vitro and in vivo. Thus targeting miR569 could potentially benefit patients with the 3q26.2 amplicon and subsequent miR569 elevation.

Author List

Chaluvally-Raghavan P, Zhang F, Pradeep S, Hamilton MP, Zhao X, Rupaimoole R, Moss T, Lu Y, Yu S, Pecot CV, Aure MR, Peuget S, Rodriguez-Aguayo C, Han HD, Zhang D, Venkatanarayan A, Krohn M, Kristensen VN, Gagea M, Ram P, Liu W, Lopez-Berestein G, Lorenzi PL, Børresen-Dale AL, Chin K, Gray J, Dusetti NJ, McGuire SE, Flores ER, Sood AK, Mills GB

Authors

Pradeep Chaluvally-Raghavan PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Sunila Pradeep PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antineoplastic Agents
Breast Neoplasms
Carrier Proteins
Cell Line, Tumor
Cell Proliferation
Cell Survival
Chromosomes, Human, Pair 3
Cisplatin
Female
Gene Amplification
Gene Duplication
Gene Expression Regulation, Neoplastic
Heat-Shock Proteins
Humans
Mice
Mice, Nude
MicroRNAs
Neoplasms, Experimental
Neoplasms, Glandular and Epithelial
Nuclear Proteins
Ovarian Neoplasms
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a