miRNA551b-3p 通过激活致癌信号模块促进三阴性乳腺癌进展。
miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer.
机构信息
Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
出版信息
Cell Rep. 2019 Dec 24;29(13):4389-4406.e10. doi: 10.1016/j.celrep.2019.11.085.
Genomic amplification of 3q26.2 locus leads to the increased expression of microRNA 551b-3p (miR551b-3p) in triple-negative breast cancer (TNBC). Our results demonstrate that miR551b-3p translocates to the nucleus with the aid of importin-8 (IPO8) and activates STAT3 transcription. As a consequence, miR551b upregulates the expression of oncostatin M receptor (OSMR) and interleukin-31 receptor-α (IL-31RA) as well as their ligands OSM and IL-31 through STAT3 transcription. We defined this set of genes induced by miR551b-3p as the "oncostatin signaling module," which provides oncogenic addictions in cancer cells. Notably, OSM is highly expressed in TNBC, and the elevated expression of OSM associates with poor outcome in estrogen-receptor-negative breast cancer patients. Conversely, targeting miR551b with anti-miR551b-3p reduced the expression of the OSM signaling module and reduced tumor growth, as well as migration and invasion of breast cancer cells.
3q26.2 基因座的基因组扩增导致三阴性乳腺癌（TNBC）中 microRNA 551b-3p（miR551b-3p）的表达增加。我们的结果表明，miR551b-3p 在 importin-8（IPO8）的帮助下转移到细胞核，并激活 STAT3 转录。结果，miR551b 通过 STAT3 转录上调了肿瘤坏死因子受体（OSMR）和白细胞介素 31 受体-α（IL-31RA）及其配体 OSM 和 IL-31 的表达。我们将这组由 miR551b-3p 诱导的基因定义为“肿瘤坏死因子信号模块”，它为癌细胞提供致癌的依赖性。值得注意的是，OSM 在 TNBC 中高度表达，而 OSM 的高表达与雌激素受体阴性乳腺癌患者的不良预后相关。相反，用抗 miR551b-3p 靶向 miR551b 可降低 OSM 信号模块的表达，减少乳腺癌细胞的肿瘤生长、迁移和侵袭。
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