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首页> 外文期刊>Biology Open >hsa-miR29b, a critical downstream target of non-canonical Wnt signaling, plays an anti-proliferative role in non-small cell lung cancer cells via targeting MDM2 expression
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hsa-miR29b, a critical downstream target of non-canonical Wnt signaling, plays an anti-proliferative role in non-small cell lung cancer cells via targeting MDM2 expression

机译：hsa-miR29b，非经典Wnt信号的关键下游靶标，通过靶向MDM2表达在非小细胞肺癌细胞中发挥抗增殖作用

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In non-small cell lung cancer cell lines, activation of β-catenin independent signaling, via Wnt7a/Frizzled9 signaling, leads to reversal of cellular transformation, reduced anchorage-independent growth and induction of epithelial differentiation. miRNA expression profiling on a human lung adenocarcinoma cell line (A549) identified hsa-miR29b as an important downstream target of Wnt7a/Frizzled9 signaling. We show herein that hsa-miR29b expression is lost in non-small cell lung cancer (NSCLC) cell lines and stimulation of β-catenin independent signaling, via Wnt7a expression, in NSCLC cell lines results in increased expression of hsa-miR29b. Surprisingly, we also identify specific regulation of hsa-miR29b by Wnt7a but not by Wnt3, a ligand for β-catenin-dependent signaling. Interestingly, knockdown of hsa-miR29b was enough to abrogate the tumor suppressive effects of Wnt7a/Frizzled9 signaling in NSCLC cells, suggesting that hsa-miR29b is an important mediator of β-catenin independent signaling. Finally, we show for the first time that hsa-miR29b plays an important role as a tumor suppressor in lung cancer by targeting murine double mutant 2 (MDM2), revealing novel nodes for Wnt7a/Frizzled9-mediated regulation of NSCLC cell proliferation.
机译：在非小细胞肺癌细胞系中，经由Wnt7a / Frizzled9信号传导的β-catenin独立信号传导的激活，导致细胞转化的逆转，锚定非依赖性生长的减少和上皮分化的诱导。在人肺腺癌细胞系（A549）上的miRNA表达谱鉴定为hsa-miR29b是Wnt7a / Frizzled9信号传导的重要下游靶标。我们在此显示非小细胞肺癌（NSCLC）细胞系中hsa-miR29b的表达丢失，并且通过Wnt7a表达刺激β-catenin独立信号传导在NSCLC细胞系中导致hsa-miR29b的表达增加。出乎意料的是，我们还确定了Wnt7a对hsa-miR29b的特异性调控，而不是由Wnt3（β-连环蛋白依赖性信号传导的配体）调控。有趣的是，敲低hsa-miR29b足以消除NSCLC细胞中Wnt7a / Frizzled9信号转导的肿瘤抑制作用，表明hsa-miR29b是β-catenin独立信号转导的重要介体。最后，我们首次展示了hsa-miR29b通过靶向鼠类双突变体2（MDM2）在肺癌中起着重要的抑癌作用，揭示了Wnt7a / Frizzled9介导的NSCLC细胞增殖调控的新节点。

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