Department of Urology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China.
Department of Critical Care Medicine, Hospital of Southern Theatre Command of PLA, Guangzhou, China.
Mol Carcinog. 2024 Jan;63(1):160-172. doi: 10.1002/mc.23643. Epub 2023 Oct 3.
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.
蛋白激酶，膜相关酪氨酸/苏氨酸 1（PKMYT1）与肿瘤的进展有关，在多种癌症中上调。然而，其在膀胱癌（BLCA）中的表达及其潜在的分子机制仍不清楚。在这里，我们发现 PKMYT1 在 BLCA 中的表达明显升高，与低表达相比，其预后较差。PKMYT1 的敲低显著抑制了 BLCA 细胞在体内和体外的增殖，以及迁移和侵袭，减少了细胞周期中的 G2/M 期并诱导了细胞凋亡。在机制上，YAP 和 TEAD1 的敲低抑制了 BLCA 细胞中 PKMYT1 的表达，而 YAP 的过表达上调了 PKMYT1 的表达，并且 YAP 通过 TEAD1 介导的直接结合到 PKMYT1 启动子上促使 PKMYT1 的转录表达。总之，这些发现表明，PKMYT1 作为 YAP/TEAD1 调节的直接靶基因，可作为 BLCA 进展和预后的潜在指标。此外，PKMYT1 可能成为 BLCA 的一种新的治疗靶点。
