Luo Jiaquan, Wang Xuhua, Chen Zhaoyuan, Zhou Huaqiang, Xiao Yihui
Department of Spine Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province 341099, China.
J Bone Oncol. 2023 Feb 17;39:100471. doi: 10.1016/j.jbo.2023.100471. eCollection 2023 Apr.
Osteosarcoma (OS) is the most malignant bone tumor which mainly occurs in childhood or adolescence. The previous studies indicated that OS is difficult to treat. KIAA1429 is one of the components of m6A complex that regulating the process of m6A modification, which plays a crucial role in tumorigenesis. But the mechanism of KIAA1429 regulating OS cell identity was not entirely clear, which needs further investigate. RT-qPCR and western blotting were applied to determine KIAA1429 expression station in OS cells and tissues. To further detect the KIAA1429 function in OS cells, the ability of proliferation, migration and invasion were analyzed by Edu, wound-healing and transwell experiments respectively. Besides, RNA sequencing was also used to further find the downstream of KIAA1429 regulation and small molecule inhibitor was added to explore the specific role of signaling pathway. Our data found that KIAA1429 is up-regulated in human OS cell lines compared to the human osteoblast cells. Meanwhile, the deletion of KIAA1429 significantly decreased cell proliferation, migration, and invasion. Interestingly, the JAK2/STAT3 signal pathway was involved in KIAA1429 regulation on OS cell characters. The KIAA1429 eliminated OS cells exhibited a decreased activity of JAK2/STAT3 signal. And the addition of JAK2/STAT3 stimulator (colivelin) could distinctly rescue the decreased OS cells' proliferation, migration, and invasion upon KIAA1429 knockdown. In summary, these data demonstrated that KIAA1429/JAK2/STAT3 axis may a new target for OS therapy.
骨肉瘤（OS）是最恶性的骨肿瘤，主要发生在儿童或青少年时期。先前的研究表明，骨肉瘤难以治疗。KIAA1429是m6A复合体的组成成分之一，参与调控m6A修饰过程，在肿瘤发生中起关键作用。但KIAA1429调控骨肉瘤细胞特性的机制尚不完全清楚，需要进一步研究。采用RT-qPCR和蛋白质免疫印迹法检测骨肉瘤细胞和组织中KIAA1429的表达情况。为进一步检测KIAA1429在骨肉瘤细胞中的功能，分别通过Edu实验、伤口愈合实验和Transwell实验分析细胞的增殖、迁移和侵袭能力。此外，还利用RNA测序进一步寻找KIAA1429调控的下游分子，并添加小分子抑制剂探索信号通路的具体作用。我们的数据发现，与人类成骨细胞相比，KIAA1429在人类骨肉瘤细胞系中表达上调。同时，敲除KIAA1429可显著降低细胞的增殖、迁移和侵袭能力。有趣的是，JAK2/STAT3信号通路参与了KIAA1429对骨肉瘤细胞特性的调控。敲除KIAA1429的骨肉瘤细胞中JAK2/STAT3信号活性降低。添加JAK2/STAT3激动剂（可利韦林）可明显挽救敲低KIAA1429后骨肉瘤细胞增殖、迁移和侵袭能力的下降。总之，这些数据表明KIAA1429/JAK2/STAT3轴可能是骨肉瘤治疗的新靶点。
