Department of Oncology, Maternal and Child Health Care Hospital of Zibo, Zibo 255029, China.
Human Resources Department, Zibo Central Hospital, Zibo 255036, China.
Biomed Res Int. 2021 May 15;2021:5596014. doi: 10.1155/2021/5596014. eCollection 2021.
Osteosarcoma is the most common type of bone malignancy, and the pathogenesis has not been entirely elucidated yet. An important deimination modification enzyme PADI4 (peptidylarginine deiminase 4) has attracted much attention in recent years for its important function in several kinds of human tumors. However, the role of PADI4 on osteosarcoma tumorigenesis remains largely unrevealed. Here, we first assessed the effect of PADI4 on osteosarcoma proliferation by the CCK8 method and colony formation assay. Ectopically expressing PADI4 positively regulates the colony formation capacity of both U2OS and Saos-2 cells. Furthermore, we explored the related mechanism and showed that PADI4 could stimulate Wnt/-catenin and MEK/ERK signaling in both U2OS and Saos-2 cells. Then, we detected expression of PADI4 in human tissues of osteosarcoma and revealed that differential expression of PADI4 was associated with tumorigenesis of osteosarcoma. Last, we performed the experiment in nude mice and results also showed PADI4 could affect the tumor growth. In conclusion, this work revealed that PADI4 could upregulate the proliferation of osteosarcoma, mainly via the Wnt/-catenin and MEK/ERK signaling pathway. This study gives us new insight into the regulation mechanism of osteosarcoma proliferation and highlights PADI4 as a promising target for osteosarcoma diagnosis and treatment.
骨肉瘤是最常见的骨恶性肿瘤，其发病机制尚未完全阐明。近年来，一种重要的脱亚氨基修饰酶 PADI4（肽基精氨酸脱亚氨酶 4）因其在几种人类肿瘤中的重要功能而引起了广泛关注。然而，PADI4 对骨肉瘤肿瘤发生的作用在很大程度上仍未被揭示。在这里，我们首先通过 CCK8 法和集落形成实验评估了 PADI4 对骨肉瘤增殖的影响。过表达 PADI4 可正向调节 U2OS 和 Saos-2 细胞的集落形成能力。此外，我们还探讨了相关机制，并表明 PADI4 可刺激 U2OS 和 Saos-2 细胞中的 Wnt/-catenin 和 MEK/ERK 信号通路。然后，我们检测了 PADI4 在人骨肉瘤组织中的表达，并揭示了 PADI4 的差异表达与骨肉瘤的发生有关。最后，我们在裸鼠中进行了实验，结果也表明 PADI4 可影响肿瘤的生长。总之，这项工作揭示了 PADI4 可上调骨肉瘤的增殖，主要通过 Wnt/-catenin 和 MEK/ERK 信号通路。本研究为骨肉瘤增殖的调控机制提供了新的见解，并突出了 PADI4 作为骨肉瘤诊断和治疗有希望的靶标。
