N6-methyladenosine-modifying enzymes are deregulated in multiple myeloma

Year 2020, 2020 Özel Sayı, 18 - 23, 26.02.2020

Dilara Akçora Yıldız

https://doi.org/10.18663/tjcl.489326

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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