Potential role of m6A RNA methylation regulators in osteosarcoma and its clinical prognostic value

Abstract

Background Osteosarcoma is a disease with high mortality in children and adolescents, and metastasis is one of the important clinical features of osteosarcoma. N6-Methyladenosine (m6A) is the most abundant methylation modification in mRNA, which is regulated by m6A regulators. It is reported that it is related to the occurrence and development of tumors. However, the mechanism of its action in osteosarcoma is rarely known. The purpose of this study was to identify the potential role of m6A regulatory factor in osteosarcoma and its clinical prognostic value. Methods Here, we used The Cancer Genome Atlas (TCGA) to comprehensively analyze the relationship between m6A regulatory factors and osteosarcoma (metastasis group and non-metastasis group). We analyzed their survival relationship and analyzed all the m6A regulatory factors in TCGA tumor data set by using the univariate Cox proportional hazard regression model. Finally, we selected two survival-related methylation regulators (FTO and IGF2BP2) as risk gene signature. Results According to the median risk, patients were divided into low-risk group and high-risk group. Multivariate Cox regression analysis showed that these two risk genes were considered to be the key factors independently predicting the prognosis of patients with osteosarcoma. In addition, we verified their characteristics with gene expression omnibus (GEO) DataSets and confirmed that they are related to tumor and immune-related signaling pathways through gene set enrichment analysis (GESA) and immune infiltration analysis. Conclusions In conclusion, m6A regulators might play an important role in the metastasis of osteosarcoma and have potential important value for the prognosis and treatment strategy of osteosarcoma patients.

m6A-dependent upregulation of TRAF6 by METTL3 is associated with metastatic osteosarcoma

“…The m6A methyltransferase METTL3 has been reported to promote the progression of various cancers, including bladder cancer and lung cancer, through modulating the expression of microRNAs or mRNAs [25] , [26] . The similar mechanism was observed in OS as well [27] , [28] , [29] , [30] , [31] . In this study, through m6A-seq, we revealed that the m6A enrichment region was distributed around the exon, while METTL3 poorly expressing OS cells showed more deposition of m6A in the 5′UTR and 3′UTR.…”

Fat mass and obesity associated (FTO)-mediated N6-methyladenosine modification of Krüppel-like factor 3 (KLF3) promotes osteosarcoma progression

“…ALKBH5 attenuates the m6A modification of PVT1 mRNA and impedes the binding of YTHDF2 to PVT1 mRNA, which increases PVT1 expression and accelerates OS growth in vivo [ 13 ]. In addition, m6A-related enzymes are involved in regulating the pluripotency of OS stem cells [ 31 , 32 ]. All these imply potential roles of m6A methylation in tumorigenesis and progression of OS.…”

N6-Methyladenosine RNA Modification in the Tumor Immune Microenvironment: Novel Implications for Immunotherapy

“…Numbers of most of the immune cells (type M1 and M2 macrophages, CD8+ T cells, Tregs, and dendritic cells) were negatively associated with IGF2BP2 expression in osteosarcoma ( 146 ). M 6 A modification-mediated aberrant activation of cell cycle-related pathways and suppression of immune response may play a crucial role in the progression of osteosarcoma ( 147 ).…”