PKMYT1 induced by YAP/TEAD1 gives rise to the progression and worse prognosis of bladder cancer
PKMYT1 induced by YAP/TEAD1 gives rise to the progression and worse prognosis of bladder cancer
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DOI：
10.1002/mc.23643
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发表时间：
2023-10
影响因子：
4.6
通讯作者：
Maoyu Wang;Chen Zhang;Yidie Ying;Meimian Hua;Fang Meng;Ziwei Wang;Anwei Liu;Shuxiong Zeng
中科院分区：
文献类型：
--
作者：
Maoyu Wang;Chen Zhang;Yidie Ying;Meimian Hua;Fang Meng;Ziwei Wang;Anwei Liu;Shuxiong Zeng
与肿瘤进展相关的蛋白激酶，膜相关酪氨酸/苏氨酸1（PKMYT 1）在多种癌症中上调。然而，它的表达和潜在的分子机制在膀胱癌（BLCA）的背景下仍然难以捉摸。我们发现PKMYT 1在BLCA中的表达明显高于低表达，与预后不良相关。PKMYT 1基因的敲除可显著抑制BLCA细胞的体内外增殖、迁移和侵袭，减少细胞周期G2/M期，诱导细胞凋亡。在BLCA细胞中，雅普和TEAD 1敲低抑制PKMYT 1表达，而过表达雅普上调PKMYT 1表达，雅普通过TEAD 1介导的直接结合PKMYT 1启动子促进PKMYT 1转录表达。总的来说，这些研究结果表明，PKMYT 1，作为一个直接的基因靶调控的雅普/TEAD 1，可以作为一个潜在的指标，在BLCA的进展和预后。PKMYT 1可能成为BLCA的一个新的治疗靶点。
Protein kinase, membrane‐associated tyrosine/threonine 1 (PKMYT1), which is associated with progression of tumor, is upregulated in a variety of cancers. However, its expression and the underlying molecular mechanisms in the context of bladder cancer (BLCA) remain elusive. Here we found that PKMYT1 expression was markedly higher expression in BLCA, which was correlated with poorer prognosis compared with low expression. Knockdown of PKMYT1 significantly inhibited the BLCA cells proliferation in vivo and in vitro, and migration and invasion, reduced G2/M phase in cell cycle and induced apoptosis. Mechanically, YAP and TEAD1 knockdown suppressed PKMYT1 expression in BLCA cells, whereas overexpression of YAP upregulated PKMYT1 expression and YAP prompted PKMYT1 transcriptional expression via TEAD1‐mediated direct binding to PKMYT1 promotor. Collectively, these findings suggest that PKMYT1, functioning as a direct gene target regulated by YAP/TEAD1, could serve as a potential indicator of progression and prognosis in BLCA. Further, PKMYT1 could serve as a novel therapeutic target for BLCA.