Clinical Significance And Potential Mechanisms of The RNA Methyltransferase KIAA1429 In Osteosarcoma

Abstract

Background: KIAA1429, a member of the RNA methyltransferase complex, is involved in cancer progression. However, the clinical significance of KIAA1429 in osteosarcoma (OS) and the underlying mechanisms by which it contributes to disease progression remain unclear. Methods: The clinical significance of KIAA1429 in OS was evaluated based on the RT-qPCR, microarray, RNA sequencing, and published data. Two lentivirus-mediated KIAA1429-targeting siRNA constructs were transfected into SW1353 cells, and CCK-8 and flow cytometry assays were applied to investigate the biological function of KIAA1429 in OS cells. KIAA1429-related genes in OS were identified from lists of co-expressed genes (CEGs) and differentially expressed genes (DEGs). Functional enrichment analysis was employed to explore the potential mechanisms by which KIAA1429 contributes to the progression of OS.Results: The mRNA expression of KIAA1429 was notably overexpressed in 250 OS samples than 71 non-cancer samples (SMD=0.74). SROC curve analysis showed that KIAA1429 exhibits diagnostic capacity between OS samples and non-cancer samples (AUC=0.83). Survival analysis showed that overexpression of KIAA1429 was associated with shorter overall survival time. Knocking down KIAA1429 reduced the level of m6A methylation, inhibited proliferation, and accelerated apoptosis in OS cells. A total of 395 KIAA1429-related genes were identified, and were enriched in the cell cycle pathway. Protein–protein interaction (PPI) network analysis showed that CDK1, CCNA2, and CCNB1 were KIAA1429-related genes that act as major network hubs in OS. Conclusion: KIAA1429 plays an oncogenic role in OS and may facilitate the progression of OS through a mechanism involving the regulation of CDK1, CCNA2, and CCNB1.