Musashi2 promotes the development and progression of pancreatic cancer by down-regulating Numb protein.
Musashi2 promotes the development and progression of pancreatic cancer by down-regulating Numb protein.
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Musashi2通过下调Numb蛋白促进胰腺癌的发生和进展
DOI：
10.18632/oncotarget.8736
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发表时间：
2017-02-28
期刊：
影响因子：
--
通讯作者：
Dong Q
中科院分区：
文献类型：
--
作者：
Sheng W;Dong M;Chen C;Li Y;Liu Q;Dong Q
Musashi2-Numb相互作用在髓系白血病的进展中起着至关重要的作用。然而，它在实体癌症中的潜在作用很少有报道。我们研究了Musashi2-Numb在胰腺癌(PC)体内外发展过程中的协同作用。PC组织中Musashi2蛋白和mRNA水平均高于配对正常胰腺组织(P<；0.05)。Musashi2过表达和Numb阳性表达分别与肿瘤大小和UICC分期呈正相关和负相关(P<；0.05)。多变量分析确定Musashi2和Numb是预测PC患者生存的不利和有利的独立指标。此外，Musashi2高表达伴Numb阴性表达的患者总体生存率显著降低(P=0.001)。在PC组织和细胞水平上，Musashi2与Numb均呈负相关。这两种内源性蛋白可以从PC细胞系中免疫共沉淀，而Musashi2在体内外抑制上调的Numb蛋白。同时，它的沉默在体外减少了细胞的侵袭和迁移，在体内抑制了皮下肿瘤的生长和肝转移的发生。然而，Numb基因敲除显著逆转了Musashi2沉默引起的细胞侵袭和迁移的减少。Musashi2通过下调Numb蛋白促进胰腺癌的发生发展。Musashi2-Numb的相互作用在PC的发展和进展中起着重要作用。
Musashi2-Numb interaction plays a vital role in the progression of myeloid leukemia. However, its potential role in solid cancers has rarely been reported. We investigated the coordinate function of Musashi2-Numb in the development of pancreatic cancer (PC) in vitro and vivo. Both Musashi2 protein and mRNA levels were higher in PC tissues than that in paired normal pancreas (P<0.05). Musashi2 overexpression and Numb positive expression were positively and negatively associated with tumor size and UICC stage, respectively (P<0.05). Multivariate analysis identified Musashi2 and Numb as adverse and favorable independent indicators for the survival of PC patients. Moreover, patients with high Musashi2 expression combining with negative Numb expression had a significantly worse overall survival (P=0.001). The negative relationship between Musashi2 and Numb was found at both PC tissue and cell levels. These two endogenous proteins can be co-immunoprecipitated from PC cell lines, and Musashi2 silence up-regulated Numb protein in vitro and vivo. Meanwhile, its silence decreased cell invasion and migration in vitro and inhibited the growth of subcutaneous tumors and the frequency of liver metastasis in vivo. However, Numb knockdown significantly reversed the decrease of cell invasion and migration induced by Musashi2 silence. Musashi2 promotes the development and progression of pancreatic cancer by down-regulating Numb protein. The interaction of Musashi2-Numb plays a significant role in the development and progression of PC.