miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer
miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer
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DOI：
10.1016/j.celrep.2019.11.085
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发表时间：
2019-12-24
期刊：
影响因子：
8.8
通讯作者：
Chaluvally-Raghavan, Pradeep
中科院分区：
文献类型：
--
作者：
Parashar, Deepak;Geethadevi, Anjali;Chaluvally-Raghavan, Pradeep
3q26.2基因座的基因组扩增导致microRNA 551 b-3 p（miR 551 b-3 p）在三阴性乳腺癌（TNBC）中的表达增加。我们的研究结果表明，miR 551 b-3 p在输入蛋白-8（IPO 8）的帮助下易位到细胞核并激活STAT 3转录。因此，miR 551 b通过STAT 3转录上调制瘤素M受体（OSMR）和白细胞介素-31受体-α（IL-31 RA）以及它们的配体OSM和IL-31的表达。我们将这组由miR 551 b-3 p诱导的基因定义为“制瘤素信号模块”，它在癌细胞中提供致癌成瘾。值得注意的是，OSM在TNBC中高度表达，OSM的表达升高与雌激素受体阴性乳腺癌患者的不良结局相关。相反，用抗miR 551 b-3 p靶向miR 551 b降低了OSM信号传导模块的表达，并降低了肿瘤生长以及乳腺癌细胞的迁移和侵袭。
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-alpha (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.