1. Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
2. Department of Radiology, The First Affiliated Hospital, Guangxi Medical University, Shuangyong Road 6, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
3. Trauma Microsurgical Hand Surgery, Guangxi Zhuang Autonomous Region People's Hospital, Taoyuan Road 6, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
4. Department of Osteology, The Second People's Hospital of Nanning, The Third Affiliated Hospital of Guangxi Medical University, Dancun Road 13, Nanning 530031, Guangxi, China.
# Yu Sun and Yi-wu Lei contributed equally to this work and should be considered co-first authors.
Background: KIAA1429, a member of the RNA methyltransferase complex, is involved in cancer progression; however, the clinical significance and underlying mechanism of KIAA1429 in osteosarcoma (OS) remains to be reported.
Methods: We evaluated the clinical significance of KIAA1429 in OS by performing RT-qPCR, microarray, and RNA sequencing and using published data as a reference. Two KIAA1429-targeting siRNA constructs were transfected into SW1353 cells. CCK-8 assay, colony formation assays, flow cytometry and the xenograft mouse model were conducted to investigate the biological function of KIAA1429 in OS.
Results: The mRNA expression of KIAA1429 was markedly upregulated in 250 OS samples as compared to that in 71 non-cancer samples (standardized mean difference = 0.67). Summary receiver operating characteristic curve analysis revealed that KIAA1429 exhibited reliable diagnostic capacity to differentiate OS samples from non-cancer samples (area under the curve = 0.83). Further, survival analysis indicated that KIAA1429 overexpression was associated with shorter overall survival time. Knocking down KIAA1429 reduced m6A methylation levels, inhibited proliferation, prevented the growth of tumors in vivo and accelerated apoptosis of OS cells. In total, 395 KIAA1429-related genes were identified among co-expressed genes and differentially expressed genes, which were enriched in the cell cycle pathway. Protein-protein interaction network analysis showed that CDK1, CCNA2, and CCNB1 were KIAA1429-related genes, serving as major network hubs in OS.
Conclusions: Our findings indicate that KIAA1429 plays an oncogenic role in OS and potentially facilitates OS progression via a mechanism that involves regulating CDK1, CCNA2, and CCNB1.
Keywords: osteosarcoma, RNA methyltransferase, KIAA1429, oncogene.