MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT.
MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT.
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MiRNA-20b/SUFU/Wnt轴加速胃癌细胞增殖、迁移和EMT
DOI：
10.1016/j.heliyon.2021.e06695
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发表时间：
2021-04
期刊：
影响因子：
4
通讯作者：
Jin Z
中科院分区：
文献类型：
--
作者：
Peng Y;Qin Y;Zhang X;Deng S;Yuan Y;Feng X;Chen W;Hu F;Gao Y;He J;Cheng Y;Wei Y;Fan X;Ashktorab H;Smoot D;Li S;Meltzer SJ;Zhuang S;Tang N;Jin Z
既往研究发现miRNA-20b在胃癌（GC）中高表达，但其功能和机制尚不清楚。Wnt信号通路与肿瘤发生有关，在超过30%的胃癌中被激活。我们想表征miRNA-20b在调节Wnt/β-catenin信号传导和EMT方面的生物学行为。我们发现miRNA-20b抑制剂抑制Topflash/Fopflash依赖性荧光素酶活性和β-catenin核易位，从而抑制Wnt通路活性和EMT。SUFU负调控Wnt和Hedgehog信号通路，被证明是miRNA-20b的靶标。此外，进一步敲低SUFU可减轻miRNA-20b抑制对Wnt通路活性、EMT、细胞增殖/迁移和集落形成的抑制作用。综上所述，miRNA-20b是一种致癌miRNA，部分通过靶向SUFU激活Wnt通路促进GC细胞增殖、迁移和EMT。miRNA-20b， SUFU， EMT, Wnt/β-catenin。
Previous research has found that miRNA-20b is highly expressed in gastric cancer (GC), however, its function and underlying mechanism are not clear. Wnt signaling pathway, implicated in tumorigeneisis, is activated in more than 30% of GC. We would like to characterize the biological behavior of miRNA-20b in terms of modulating Wnt/β-catenin signaling and EMT. We showed that miRNA-20b inhibitors suppressed Topflash/Fopflash dependent luciferase activity and the β-catenin nuclear translocation, resulting in inhibition of Wnt pathway activity and EMT. SUFU, negatively regulating Wnt and Hedgehog signaling pathway, was proved to be targeted by miRNA-20b. Moreover, additional knockdown of SUFU alleviated the inhibitory effect on Wnt pathway activity, EMT, cell proliferation/migration and colony formation caused by miRNA-20b inhibition. In summary, miRNA-20b is an oncogenic miRNA and promoted cell proliferation, migration and EMT in GC partially by activating Wnt pathway via targeting SUFU. miRNA-20b, SUFU, EMT, Wnt/β-catenin.
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