AURKB Geni miR-34a-5p ve let-7b-5p Tarafından Hedeflendiğinden AML Hücre Proliferasyonunda Rol Oynar mı?

Amaç: Lösemik blastların çoğalarak birikimiyle karakterize olan AML’de kemik iliğindeki normal kan hücrelerinin üretimi sekteye uğradığından hastalar anemi ve trombositopeni sorunu yaşamaktadır. AML'de yüksek oranda eksprese edildiği bildirilen Aurora kinazların gen ekspresyonu azaldığında AML'deki klinik bulguları hafifletmesi mümkün olabilir. Bu çalışmada, AURKB ile protein ekspresyonunu düzenleme potansiyeli bulunan önemli miRNA’ların ilişkisinin incelenmesi amaçlanmıştır. Metod: HL60 ve NB4 hücreleri, önemli tümor supresör miRNA’lardan olan miR-34a-5p ve let-7b-5p mimikleri ile tarnsfekte edilmiştir. Ardından WST-8 tekniğiyle proliferasyona etkileri incelenmiş ve qRT-PZR ile de AURKB gen ifadesine etkileri incelenmiştir. Bulgular: Her iki AML hücre hattında da bu miRNA’ların proliferasyonu negatif yönde regüle ettiği ve kontrol grubuna kıyasla miRNA transfekte edilen grupta Aurora kinase B (AURKB) geninin ifade seviyesini dowregüle ettikleri belirlenmiştir. Sonuç: Sonuç olarak miR-34a-5p ve let-7b-5p’nin AML hücrelerinde AURKB ifadesini düzenleyebileceği tespit edilmiştir. Bu nedenle, AML’deki aşırı hücre bölünmesi ve kötü prognozun engellenebilmesinde bu miRNA’ların terapötik bir biyomarker olarak önemli bir potansiyeli olabileceği düşünülmüştür.

Anahtar Kelimeler:

AML, AURKB, miR-34a-5p, let-7b-5p

Is the AURKB Gene Involved in Aml Cell Proliferation Since It is Targeted by miR-34a-5p and let-7b-5p?

Objective: The production of normal blood cells in the bone marrow is interrupted in AML, which is characterized by the proliferation and accumulation of leukemic blasts. Therefore, patients experience anemia and thrombocytopenia. When gene expression of Aurora kinases, which is reported to be highly expressed in AML, decreases, it may be possible to alleviate the clinical findings in AML. In this study, it was aimed to examine the relationship of AURKB with important miRNAs that have the potential to regulate gene expression. Method: HL60 and NB4 cells were transfected with important tumor suppressor miRNAs miR-34a-5p and let-7b-5p mimics. Then, its effects on proliferation were examined with WST-8 technique and its effects on AURKB gene expression were examined with qRT-PCR. Results: It was determined that these miRNAs negatively regulated proliferation in both AML cell lines and downregulated the expression level of the Aurora kinase B (AURKB) gene in the miRNA transfected group compared to the control group. Conclusion: In conclusion, it was determined that miR-34a-5p and let-7b-5p could regulate AURKB expression in AML cells. Therefore, it was thought that these miRNAs may have an important potential as a therapeutic biomarker in preventing excessive cell division and poor prognosis in AML.

Keywords:

AML, AURKB, miR-34a-5p, let-7b-5p,

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ISSN: 1309-3878
Yayın Aralığı: Yılda 3 Sayı
Başlangıç: 2009
Yayıncı: Düzce Üniversitesi Tıp Fakültesi Aile Hekimliği AD adına Yrd.Doç.Dr.Cemil Işık Sönmez