The m(6)A methyltransferase WTAP plays a key role in the development of diffuse large B-cell lymphoma via regulating the m(6)A modification of catenin beta 1

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most frequently occurring subtype of lymphoma. Unfortunately, the fundamental processes underlying the pathogenesis of DLBCL remain little understood. N(6)-methyladenosine (m(6)A) methylation has been shown to be the most common internal alteration of mRNAs found in eukaryotes, and it is thought to play a key role in cancer pathogenesis. However, the precise relationship between m(6)A mRNA methylation and DLBCL pathogenesis remains to be fully elucidated. METHODS: The mRNA and protein expression of Wilms tumor 1-associating protein (WTAP) were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis in lymphoma cells lines. The effects of WTAP expression on human lymphoma cells lines were assessed using cell proliferation assays, colony formation assays, and CCK8 assays. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to screen candidate gene targets of WTAP. Finally, the regulatory mechanisms of WTAP in DLBCL were investigated using methylated RNA immunoprecipitation (MeRIP) assays. RESULTS: This study investigated the precise function of WTAP in DLBCL formation. The results demonstrated that the levels of m(6)A RNA methylation and WTAP expression were both elevated in DLBCL cell lines and tissues. Downregulation of WTAP expression in DLBCL cells caused a reduction in cell growth in a functional sense. WTAP knockdown reduced catenin beta 1 (CTNNB1) m(6)A methylation and CTNNB1 total mRNA levels. Furthermore, CTNNB1 overexpression eliminated the WTAP-induced reduction of cell growth in DLBCL cells. CONCLUSIONS: In conclusion, these findings demonstrated that WTAP promotes DLBCL development via modulation of m(6)A methylation in CTNNB1.