Psychological distress of nurses in Taiwan who worked during the outbreak of SARS.

OBJECTIVE

Osteosarcoma (OS) is a malignant tumor originating from osteoblasts. Methyltransferase-like 14 (METTL14) is an N6-methyladenosine (m6A) methyltransferase that has been reported to promote OS progression; however, its underlying mechanism remains unclear.

METHODS

Gene Expression Omnibus (GEO), RNA modification base version 3.0 (RMbase V3.0), RNA modification variant database (RMvar), RNA modification disease database version 2.0 (RMDisease V2.0), sequence-based RNA adenosine methylation site predictor (SRAMP), the encyclopedia of RNA interactomes (ENCORI), and RNA binding protein map (RBPmap) were used to obtain gene expression and modification information related to OS. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) were used to detect gene expression at the transcriptional and translational levels. Cell transfection was used to knock down or overexpress target genes. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to measure cell viability. Flow cytometry was used to detect cell apoptosis. The Transwell assay was used to evaluate cell migration. Sphere formation assay assessed stemness characteristics. Tube formation assay evaluated angiogenic capability. RNA immunoprecipitation (RIP) was used to detect interactions between proteins and messenger RNA (mRNA).

RESULTS

METTL14 was highly expressed in OS-related cells. Knockdown of METTL14 reduced cell viability, increased apoptosis, and suppressed cell migration, stemness, and angiogenic capacity. In addition, METTL14 cooperated with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to mediate m6A methylation of integrin subunit beta 3 (ITGB3), thereby promoting the malignant behaviors of OS-related cells.

CONCLUSION

METTL14 and IGF2BP1 mediate the m6A methylation of ITGB3, further promoting the deterioration of OS, providing new insights into the molecular mechanisms and potential therapeutic targets of OS.