It has been reported that cyclin-dependent kinase like 3 (CDKL3) plays a crucial role in cell proliferation and migration in several cancers. However, the function of CDKL3 in triple-negative breast cancer (TNBC) is still unclear. In the present study, immunohistochemistry (IHC) was conducted to detect the CDKL3 expression. CCK-8, flow cytometry, Transwell assays, and mice xenograft models, were performed to explore the roles of CDKL3 on the proliferation and migration of TNBC in vitro and in vivo. Besides, protein chip analysis was used to screen the potential pathways, which was further confirmed by promoter activity assay, western blotting, and CCK-8 assay. Our findings reveal a high expression of CDKL3 in TNBC tissues, which is closely related to a poor prognosis of patients with TNBC. In TNBC cells, CDKL3 knockdown inhibits cell proliferation and migration, whereas CDKL3 overexpression has exactly the opposite effect. Consistently, CDKL3 knockdown induces cell apoptosis in vitro but suppresses tumor growth in vivo. Furthermore, CDKL3 knockdown increases p53 expression and reduces cell viability, and these effects are significantly weakened by the p53 inhibitor, PFT-α. In conclusion, the current study highlights that CDKL3 promotes TNBC progressions via regulating the p53 signaling pathway, suggesting that CDKL3 is a novel therapeutic target for TNBC treatment.

中文翻译：

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细胞周期蛋白依赖性激酶如 3 通过抑制 p53 信号通路促进三阴性乳腺癌进展。

据报道，细胞周期蛋白依赖性激酶 3 (CDKL3) 在几种癌症的细胞增殖和迁移中起关键作用。然而，CDKL3 在三阴性乳腺癌 (TNBC) 中的作用仍不清楚。在本研究中，进行免疫组织化学（IHC）检测CDKL3的表达。进行 CCK-8、流式细胞术、Transwell 检测和小鼠异种移植模型，以探索 CDKL3 在体外和体内 TNBC 增殖和迁移中的作用。此外，蛋白质芯片分析用于筛选潜在途径，并通过启动子活性测定、蛋白质印迹和CCK-8测定进一步证实。我们的研究结果揭示了 CDKL3 在 TNBC 组织中的高表达，这与 TNBC 患者的预后不良密切相关。在 TNBC 细胞中，CDKL3 敲低抑制细胞增殖和迁移，而 CDKL3 过表达具有完全相反的效果。一致地，CDKL3 敲低在体外诱导细胞凋亡，但在体内抑制肿瘤生长。此外，CDKL3 敲低会增加 p53 表达并降低细胞活力，而 p53 抑制剂 PFT-α 会显着削弱这些作用。总之，目前的研究强调 CDKL3 通过调节 p53 信号通路促进 TNBC 进展，表明 CDKL3 是 TNBC 治疗的新治疗靶点。p53抑制剂PFT-α显着削弱了这些作用。总之，目前的研究强调 CDKL3 通过调节 p53 信号通路促进 TNBC 进展，表明 CDKL3 是 TNBC 治疗的新治疗靶点。p53抑制剂PFT-α显着削弱了这些作用。总之，目前的研究强调 CDKL3 通过调节 p53 信号通路促进 TNBC 进展，表明 CDKL3 是 TNBC 治疗的新治疗靶点。