N6-methyladenosine-modifying enzymes are deregulated in multiple myeloma

Abstract

Aim: N6-methyladenosine (m6A) mRNA modification plays essential roles in various cellular processes including regulation of gene expression. However, its role in Multiple Myeloma (MM) biology remains largely unknown. Therefore, the aim of this study is to investigate the expression levels of m6A-regulating enzymes in MM.

Material and Methods: The expression of m6A-regulating enzymes was investigated in monoclonal gammopathy of undetermined significance (MGUS), smouldering MM (SMM), MM and in their normal counterparts using publicly available Gene Expression Omnibus datasets, GSE6477 and GSE47552.

Results: By analyzing GEO DataSets GSE6477 and GSE47552, the expression levels of METTL3, METTL14 and FTO were found to be downregulated in MM, whereas no significant change was found for WTAP, ALKBH5, YTHDF1 and YTHDF2. YTHDF3 expression showed a reduction in MM based on GSE6477 data.

Conclusion: The expression of m6A-modifying genes is deregulated in MM plasma cells compared to normal plasma cells. Altered expression of m6A-modifying genes seems to play a role in the promotion of MM.

Keywords

• Multiple myeloma,epitranscriptome,m6A,gene expression,METTL3,FTO

Multipl miyelomda N6-metiladenozin modifiye edici enzimlerin düzensizliği

Abstract

Amaç: N6-metiladenozin (m6A) mRNA modifikasyonu, gen ekspresyonunun düzenlenmesi dahil olmak üzere çeşitli hücresel işlemlerde önemli rol oynamaktadır. Bununla birlikte, Multipl Miyelom (MM) biyolojisindeki rolü büyük ölçüde bilinmemektedir. Bu nedenle, bu çalışmanın amacı MM'da m6A düzenleyici enzimlerin ekspresyon düzeylerini araştırmaktır.

Gereç ve Yöntemler: M6A düzenleyici enzimlerin ekspresyonu kamuya açık Gene Expression Omnibus veri kümeleri GSE6477 ve GSE47552 kullanılarak, anlamı belirsiz monoklonal gamopati (MGUS), smouldering MM (SMM), MM ve normal muadillerinde araştırılmıştır.

Bulgular: GEO data setleri GSE6477 ve GSE47552 analiz edilerek, METTL3, METTL14 ve FTO ekspresyon seviyelerinin MM'da downregüle olduğu bulunurken WTAP, ALKBH5, YTHDF1 ve YTHDF2 için anlamlı bir değişiklik bulunmadı. YTHDF3 ifadesi, GSE6477 verisine dayalı olarak MM'de bir azalma gösterdi.

Tartışma: M6A değiştirici genlerin ifadesi, normal plazma hücrelerine kıyasla MM plazma hücrelerinde deregüle edildiği bulunmuştur. M6A'nın modifiye edici genlerinin değişmiş ifadesi, MM'nın oluşumunda rol oynar gibi görünmektedir.

Keywords

• Multipl miyelom,epitranskriptom,m6A,gen ekpresyonu,METTL3,FTO

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