MicroRNA-148a-3p suppresses epithelial-to-mesenchymal transition and stemness properties via Wnt1-mediated Wnt/β-catenin pathway in pancreatic cancer.
MicroRNA-148a-3p suppresses epithelial-to-mesenchymal transition and stemness properties via Wnt1-mediated Wnt/β-catenin pathway in pancreatic cancer.
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DOI：
10.1111/jcmm.15900
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发表时间：
2020-11
影响因子：
5.3
通讯作者：
Xiao W
中科院分区：
文献类型：
--
作者：
Fu X;Hong L;Yang Z;Tu Y;Xin W;Zha M;Tu S;Sun G;Li Y;Xiao W
虽然miR-148A-3p已被报道在多种癌症中发挥肿瘤抑制作用，但miR-148A-3p调节胰腺癌细胞上皮向间充质转化(EMT)和干细胞特性的分子机制仍不清楚。在本研究中，我们证明miR-148A-3p在PC组织和细胞系中的表达显著下调。此外，miR-148A-3p的低表达与PC患者的总生存期(OS)较差相关。体外功能获得和功能丧失实验表明，miR-148A-3p抑制PC细胞的EMT和干细胞特性，以及PC细胞的增殖、迁移和侵袭。双荧光素酶报告分析表明，WNT1是miR-148A-3p的直接靶点，其在PC组织中的表达与miR-148A-3p呈负相关。此外，miR-148A-3p通过下调WNT1抑制Wnt/β-catenin通路。WNT1过表达挽救了异位miR-148A-3p的作用。MiR-148A-3p在PC中的这些生物学功能在裸鼠移植瘤模型中也得到了证实。综上所述，这些发现提示miR-148A-3p通过抑制Wnt1介导的Wnt/β-catenin途径抑制PC细胞的增殖、侵袭、EMT和干细胞特性，可能成为PC的一个潜在的预后生物标志物和治疗靶点。
Although miR‐148a‐3p has been reported to function as a tumour suppressor in various cancers, the molecular mechanism of miR‐148a‐3p in regulating epithelial‐to‐mesenchymal transition (EMT) and stemness properties of pancreatic cancer (PC) cells remains to be elucidated. In the present study, we demonstrated that miR‐148a‐3p expression was remarkably down‐regulated in PC tissues and cell lines. Moreover, low expression of miR‐148a‐3p was associated with poorer overall survival (OS) in patients with PC. In vitro, gain‐of‐function and loss‐of‐function experiments showed that miR‐148a‐3p suppressed EMT and stemness properties as well as the proliferation, migration and invasion of PC cells. A dual‐luciferase reporter assay demonstrated that Wnt1 was a direct target of miR‐148a‐3p, and its expression was inversely associated with miR‐148a‐3p in PC tissues. Furthermore, miR‐148a‐3p suppressed the Wnt/β‐catenin pathway via down‐regulation of Wnt1. The effects of ectopic miR‐148a‐3p were rescued by Wnt1 overexpression. These biological functions of miR‐148a‐3p in PC were also confirmed in a nude mouse xenograft model. Taken together, these findings suggest that miR‐148a‐3p suppresses PC cell proliferation, invasion, EMT and stemness properties via inhibiting Wnt1‐mediated Wnt/β‐catenin pathway and could be a potential prognostic biomarker as well as a therapeutic target in PC.
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DOI：
10.1158/1078-0432.ccr-13-2947
发表时间：
2014-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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通讯作者：
Mulvihill SJ
影响因子：
2.9
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影响因子：
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