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

• 3q26.2 copy number amplification is associated with increased miR569 levels
• miR569 enhances tumor growth and metastasis
• miR569 alters expression of TP53INP1 independent of transcriptional regulation
• anti-miR569 induces cell death and sensitizes cancer cells to cisplatin

SummarySmall 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.

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