The role and mechanism of JAK2/STAT3 signaling pathway regulated by m6A methyltransferase KIAA1429 in osteosarcoma

Abstract

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.

Keywords

• Osteosarcoma
• m6A modification
• KIAA1429
• JAK2/STAT3 signal pathway