Copy Number Gain of hsa-miR-569 at 3q26.2 Leads to Loss of TP53INP1 and Aggressiveness of Epithelial Cancers

Pradeep Chaluvally-Raghavan, Fan Zhang, Sunila Pradeep, Mark P. Hamilton, Xi Zhao, Rajesha Rupaimoole, Tyler Moss, Yiling Lu, Shuangxing Yu, Chad V. Pecot, Miriam R. Aure, Sylvain Peuget, Cristian Rodriguez-Aguayo, Hee Dong Han, Dong Zhang, Avinashnarayan Venkatanarayan, Marit Krohn, Vessela N. Kristensen, Mihai Gagea, Prahlad RamWenbin Liu, Gabriel Lopez-Berestein, Philip L. Lorenzi, Anne Lise Børresen-Dale, Kwang-Yung Chin, Joe Gray, Nelson J. Dusetti, Sean E. McGuire, Elsa R. Flores, Anil K. Sood, Gordon Mills

Research output: Contribution to journalArticle

30 Scopus 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 invitro and invivo. Thus targeting miR569 could potentially benefit patients with the 3q26.2 amplicon and subsequent miR569 elevation.

Original languageEnglish (US)
Pages (from-to)863-879
Number of pages17
JournalCancer Cell
Volume26
Issue number6
DOIs
Publication statusPublished - Dec 8 2014

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ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Chaluvally-Raghavan, P., Zhang, F., Pradeep, S., Hamilton, M. P., Zhao, X., Rupaimoole, R., ... Mills, G. (2014). Copy Number Gain of hsa-miR-569 at 3q26.2 Leads to Loss of TP53INP1 and Aggressiveness of Epithelial Cancers. Cancer Cell, 26(6), 863-879. https://doi.org/10.1016/j.ccell.2014.10.010