Department of Urology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.
State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing 400038, China.
Pathol Res Pract. 2024 Jul;259:155369. doi: 10.1016/j.prp.2024.155369. Epub 2024 May 26.
Bladder cancer is a common malignancy with a poor prognosis worldwide. Positive cofactor 4 (PC4) is widely reported to promote malignant phenotypes in various tumors. Nonetheless, the biological function and mechanism of PC4 in bladder cancer remain unclear. Here, for the first time, we report that PC4 is elevated in bladder cancer and is associated with patient survival. Moreover, PC4 deficiency obviously inhibited bladder cancer cell proliferation and metastasis by reducing the expression of genes related to cancer stemness (CD44, CD47, KLF4 and c-Myc). Through RNA-seq and experimental verification, we found that activation of the Wnt5a/β-catenin pathway is involved in the malignant function of PC4. Mechanistically, PC4 directly interacts with Sp1 to promote Wnt5a transcription. Thus, our study furthers our understanding of the role of PC4 in cancer stemness regulation and provides a promising strategy for bladder cancer therapy.
膀胱癌是一种常见的恶性肿瘤，在全球范围内预后较差。阳性共因子 4（PC4）被广泛报道能促进多种肿瘤的恶性表型。然而，PC4 在膀胱癌中的生物学功能和机制仍不清楚。在这里，我们首次报道 PC4 在膀胱癌中上调，并与患者的生存有关。此外，PC4 缺失通过降低与癌症干性相关的基因（CD44、CD47、KLF4 和 c-Myc）的表达，明显抑制了膀胱癌细胞的增殖和转移。通过 RNA-seq 和实验验证，我们发现 Wnt5a/β-catenin 通路的激活参与了 PC4 的恶性功能。从机制上讲，PC4 直接与 Sp1 相互作用，促进 Wnt5a 的转录。因此，我们的研究加深了我们对 PC4 在癌症干性调控中的作用的理解，并为膀胱癌的治疗提供了一个有前景的策略。
