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. 2024 Jan 1;15(1):126-139.
doi: 10.7150/jca.86630. eCollection 2024.

Clinical Significance and Potential Mechanisms of the RNA Methyltransferase KIAA1429 in Osteosarcoma

Yu Sun  1 , Yi-Wu Lei  2 , Jia-Xing Zeng  1   3 , Lu-Yang Zhong  1 , Jian-Wei Liu  4 , Yu-Nan Man  1 , Mao-Lin He  1
Affiliations

Clinical Significance and Potential Mechanisms of the RNA Methyltransferase KIAA1429 in Osteosarcoma

Yu Sun et al. J Cancer. .

Abstract

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: KIAA1429; RNA methyltransferase; oncogene.; osteosarcoma.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
The expression level of KIAA1429 in OS based on RT-qPCR, microarray and RNA sequencing data. (A) RT-qPCR. (B) GSE99671. (C) GSE126209. (D) GSE19276. (E) GSE42352. (F) GSE87624. OS: osteosarcoma.
Figure 2
Figure 2
Diagnostic capability of KIAA1429 in OS based on RT-qPCR, microarray and RNA sequencing data. (A) RT-qPCR. (B) GSE99671. (C) GSE126209. (D) GSE19276. (E) GSE42352. (F) GSE87624. OS: osteosarcoma.
Figure 3
Figure 3
Clinical significance of KIAA1429 in OS was evaluated by meta-analysis. (A) Forest diagram of KIAA1429 expression in OS. (B) Sensitivity analysis of KIAA1429 expression in OS. (C) Begg's funnel diagram, which suggested no publication bias. (D) The sROC curve showed that KIAA1429 had a good capability to discriminate OS samples from non-cancer samples. (E) Deek's funnel diagram, which suggested no publication bias. (F) Forest plot of the effects of KIAA1429 expression on disease prognosis in OS. OS: osteosarcoma.
Figure 4
Figure 4
Biological function of KIAA1429 in OS. (A) The expression of KIAA1429 in OS cells and osteoblasts. (B) The knockdown efficiency of KIAA1429 in SW1353 cells was confirmed by western blot. (C) The knockdown efficiency of KIAA1429 in SW1353 cells was confirmed by RT-qPCR. (D) EpiQuik m6A RNA Methylation Quantification Kit was used to evaluate the content of m6A in SW1353 cells after silencing KIAA1429. (E) Cell counting kit-8 assay was performed to assess KIAA1429-knockdown on cell proliferation in SW1353 cells. (F) Silencing KIAA1429 impaired colony forming ability in SW1353 cells. (G) Flow cytometry assay was applied to determine the effects of KIAA1429-knockdown on cell apoptosis in SW1353 cells. OS: osteosarcoma. *p <0.05; **p <0.01.
Figure 5
Figure 5
OS cells tumorigenicity diminishes in vivo when KIAA1429 was knocked down. (A) The size of xenograft tumors in vivo markedly declined after KIAA1429 was knockdown. (B) After silencing KIAA1429, the OS cells transplanted into naked mice have a significantly lower volume. (C) After silencing KIAA1429, the OS cells transplanted into naked mice have a significantly lower weight. OS: osteosarcoma. *p <0.05; **p <0.01.
Figure 6
Figure 6
The screening and PPI network analysis of KIAA1429-related genes. (A) A total of 395 KIAA1429-related genes were identified from CEGs and DEGs in OS. (B) PPI network analysis showed that CDK1, CCNA2, and CCNB1 had the top three degrees of connection of the KIAA1429 related genes. CEGs: co-expressed genes; DEGs: differentially expressed genes; OS: osteosarcoma.
Figure 7
Figure 7
Functional and pathway enrichment analyses of the KIAA1429-related genes. (A) Biological process. (B) Cellular component. (C) Molecular function. (D) KEGG pathways.
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