Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Cancer Cell. 2014 Dec 8;26(6):863-879. doi: 10.1016/j.ccell.2014.10.010.
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.
小型非编码 miRNAs 是基因组异常和新兴治疗靶点的研究不足的目标。3q26.2 扩增子是包括卵巢癌和乳腺癌在内的多种癌症谱系中最常见的基因组异常之一。我们证明，hsa-miR-569（以下简称 miR569）在一部分卵巢癌和乳腺癌中过度表达，至少部分是由于 3q26.2 扩增子，改变了细胞的存活和增殖。miR569 通过下调 TP53INP1 表达，是 miR569 对存活和增殖产生影响所必需的。针对 miR569 可以通过增加体外和体内的细胞死亡，使过度表达 miR569 的卵巢癌和乳腺癌细胞对顺铂敏感。因此，针对 miR569 可能使 3q26.2 扩增子和随后 miR569 升高的患者受益。
