TY - JOUR
T1 - Copy Number Gain of hsa-miR-569 at 3q26.2 Leads to Loss of TP53INP1 and Aggressiveness of Epithelial Cancers
AU - Chaluvally-Raghavan, Pradeep
AU - Zhang, Fan
AU - Pradeep, Sunila
AU - Hamilton, Mark P.
AU - Zhao, Xi
AU - Rupaimoole, Rajesha
AU - Moss, Tyler
AU - Lu, Yiling
AU - Yu, Shuangxing
AU - Pecot, Chad V.
AU - Aure, Miriam R.
AU - Peuget, Sylvain
AU - Rodriguez-Aguayo, Cristian
AU - Han, Hee Dong
AU - Zhang, Dong
AU - Venkatanarayan, Avinashnarayan
AU - Krohn, Marit
AU - Kristensen, Vessela N.
AU - Gagea, Mihai
AU - Ram, Prahlad
AU - Liu, Wenbin
AU - Lopez-Berestein, Gabriel
AU - Lorenzi, Philip L.
AU - Børresen-Dale, Anne Lise
AU - Chin, Koei
AU - Gray, Joe
AU - Dusetti, Nelson J.
AU - McGuire, Sean E.
AU - Flores, Elsa R.
AU - Sood, Anil K.
AU - Mills, Gordon B.
N1 - Funding Information:
G.B.M. is supported by NCI (2P50CA083639-11, 5P50CA058183-17, and 5R01CA123219-01), Stand up to Cancer/American Association of Cancer Research (SU2C-AACR-DT0209), and Komen Promise Grant (KG081694). P.C.R. is supported by Ann Schreiber Program for Excellence grant from Ovarian Cancer Research Fund and Scientific scholar award from Marsha Rivkin Center for Ovarian Cancer Research. J.W.G. is supported by NCI (P50CA58207 and U54CA112970). A.K.S. is supported by NCI (P50CA083639, P50CA098258, and U54CA151668). We thank Lydia W.T. Cheung for helpful insights. We acknowledge technical help from Nitin Puri and Varun Bagai, Ambion, Life Technologies, Austin, Texas for the RNAi studies. We thank Ronny Drapkin, Marian Novak, and Alison Karst for providing RNA extracted from normal fallopian tube samples. G.B.M. received sponsored research support from AstraZeneca, GlaxoSmithKline, Celgene, Exelixis, Roche, and Wyeth/Pfizer and has served as consultant to AstraZeneca, Celgene, Enzon, Hanall Bio, Novartis, Nuevolution, Symphogen, and Wyeth/Pfizer.
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/12/8
Y1 - 2014/12/8
N2 - 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 invitro and invivo. Thus targeting miR569 could potentially benefit patients with the 3q26.2 amplicon and subsequent miR569 elevation.
AB - 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 invitro and invivo. Thus targeting miR569 could potentially benefit patients with the 3q26.2 amplicon and subsequent miR569 elevation.
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U2 - 10.1016/j.ccell.2014.10.010
DO - 10.1016/j.ccell.2014.10.010
M3 - Article
C2 - 25490449
AN - SCOPUS:84919477596
SN - 1535-6108
VL - 26
SP - 863
EP - 879
JO - Cancer Cell
JF - Cancer Cell
IS - 6
ER -