Yıl: 2020 Cilt: 30 Sayı: 2 Sayfa Aralığı: 63 - 71 Metin Dili: İngilizce DOI: 10.4999/uhod.204139 İndeks Tarihi: 19-11-2020

The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells

Öz:
The promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) fusion gene is present in 98% of the patients with acute promyelocytic leukemia (APL), the M3 subtype of acute myeloid leukemia (AML). All-trans retinoic acid (ATRA) is widely used to treat patientswith APL. Nucleolar Protein 7 (NOL7) is a tumor suppressor gene regulated by retinoid X receptor (RXR). The 6p23 chromosomalregion, where NOL7 is located, is associated with many cancers, including AML. Here, we aimed to investigate the effect of NOL7 intwo AML cell lines (the PML-RARA-positive NB4 cell line and the PML-RARA-negative HL60 cell line) and in the resistance to ATRA.For this purpose, we knocked down NOL7 expression by using short interfering RNA (siRNA) and stimulated the cells with ATRA.Apoptosis, cell viability, proliferation, and granulocytic differentiation analyses were performed. Our findings show that granulocytic differentiation was blocked in ATRA-treated NB4 cells 24 hours after NOL7 siRNA transfection when the expression of NOL7 had beenreduced by 81%. Downregulation of NOL7 had no apparent effect on the cellular proliferation and apoptosis. Our study suggests thatATRA-induced granulocytic differentiation is inhibited in NOL7-downregulated NB4 cells. These results suggest that NOL7 expressioncontributes to ATRA-induced granulocytic differentiation and loss of NOL7 might be involved in the development of ATRA resistance
Anahtar Kelime:

All-Trans Retinoik Asit ile İndüklenen Akut Promiyelositik Lösemi Hücrelerinde NOL7’nin Rolü

Öz:
Akut promiyelositik lösemi (APL), akut miyeloid löseminin (AML) M3 alttipi olarak sınıflandırılmaktadır. APL hastalarının %98’inde PMLRARA füzyon geni bulunmaktadır. APL tedavisinde sıklıkla all-trans retinoik asit (ATRA) kullanılmaktadır. Nükleolar Protein 7 (NOL7) geni Retinoid X Reseptör (RXR) tarafından düzenlenen tümör baskılayıcı bir gendir. 6p23 bölgesinde bulunan NOL7 geninin, AML’de dahil olmak üzere birçok kanser ile ilişkisi gösterilmiştir. Bu sebeplerle, AML hücre soylarında (PML-RARA füzyon geni bulunan NB4 ve bulunmayan HL60 hücre soylarında) NOL7 geninin etkisini ve ATRA’ya direnç gelişimindeki rolünü araştırmayı amaçladık. Bu amaçla, NB4 ve HL60 hücre soylarında NOL7 gen anlatımı short interfering RNA (siRNA) kullanılarak baskılandı ve ATRA ile uyarıldı. Hücre– lerde apoptoz, canlılık, proliferasyon ve granülositik farklılaşmanın analizleri yapıldı. Bulgularımıza göre, NOL7 gen anlatımının %81 oranında baskılandığı NB4 hücrelerinde 24. saatte ATRA ile indüklenen farklılaşmanın engellendiği görüldü. NOL7 baskılanmasının hücre çoğalması ve farklılaşması üzerine bariz bir etkisi görülmedi. Bu bulgular, NB4 hücrelerinde NOL7 baskılanmasının, ATRA aracılı granülositik farklılaşmayı engellendiğini göstermiştir. Bu sonuçlar, NOL7’nin ATRA ile indüklenen granülositik farklılaşmaya katkıda bulunabileceğini ve NOL7 yokluğunun ATRA direncinin gelişiminde rol oynayabileceğini düşündürmektedir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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APA EMRENCE Z, Sariman M, ABACI N, Cinar S, Salman Yaylaz B, Biberoğlu N, Cakiris A, Deniz G, Sırma Ekmekci S (2020). The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. , 63 - 71. 10.4999/uhod.204139
Chicago EMRENCE ZELIHA,Sariman Melda,ABACI NESLIHAN,Cinar Suzan,Salman Yaylaz Burcu,Biberoğlu Nezahat Ece,Cakiris Aris,Deniz Gunnur,Sırma Ekmekci Sema The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. (2020): 63 - 71. 10.4999/uhod.204139
MLA EMRENCE ZELIHA,Sariman Melda,ABACI NESLIHAN,Cinar Suzan,Salman Yaylaz Burcu,Biberoğlu Nezahat Ece,Cakiris Aris,Deniz Gunnur,Sırma Ekmekci Sema The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. , 2020, ss.63 - 71. 10.4999/uhod.204139
AMA EMRENCE Z,Sariman M,ABACI N,Cinar S,Salman Yaylaz B,Biberoğlu N,Cakiris A,Deniz G,Sırma Ekmekci S The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. . 2020; 63 - 71. 10.4999/uhod.204139
Vancouver EMRENCE Z,Sariman M,ABACI N,Cinar S,Salman Yaylaz B,Biberoğlu N,Cakiris A,Deniz G,Sırma Ekmekci S The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. . 2020; 63 - 71. 10.4999/uhod.204139
IEEE EMRENCE Z,Sariman M,ABACI N,Cinar S,Salman Yaylaz B,Biberoğlu N,Cakiris A,Deniz G,Sırma Ekmekci S "The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells." , ss.63 - 71, 2020. 10.4999/uhod.204139
ISNAD EMRENCE, ZELIHA vd. "The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells". (2020), 63-71. https://doi.org/10.4999/uhod.204139
APA EMRENCE Z, Sariman M, ABACI N, Cinar S, Salman Yaylaz B, Biberoğlu N, Cakiris A, Deniz G, Sırma Ekmekci S (2020). The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. Uluslararası Hematoloji-Onkoloji Dergisi, 30(2), 63 - 71. 10.4999/uhod.204139
Chicago EMRENCE ZELIHA,Sariman Melda,ABACI NESLIHAN,Cinar Suzan,Salman Yaylaz Burcu,Biberoğlu Nezahat Ece,Cakiris Aris,Deniz Gunnur,Sırma Ekmekci Sema The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. Uluslararası Hematoloji-Onkoloji Dergisi 30, no.2 (2020): 63 - 71. 10.4999/uhod.204139
MLA EMRENCE ZELIHA,Sariman Melda,ABACI NESLIHAN,Cinar Suzan,Salman Yaylaz Burcu,Biberoğlu Nezahat Ece,Cakiris Aris,Deniz Gunnur,Sırma Ekmekci Sema The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. Uluslararası Hematoloji-Onkoloji Dergisi, vol.30, no.2, 2020, ss.63 - 71. 10.4999/uhod.204139
AMA EMRENCE Z,Sariman M,ABACI N,Cinar S,Salman Yaylaz B,Biberoğlu N,Cakiris A,Deniz G,Sırma Ekmekci S The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. Uluslararası Hematoloji-Onkoloji Dergisi. 2020; 30(2): 63 - 71. 10.4999/uhod.204139
Vancouver EMRENCE Z,Sariman M,ABACI N,Cinar S,Salman Yaylaz B,Biberoğlu N,Cakiris A,Deniz G,Sırma Ekmekci S The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells. Uluslararası Hematoloji-Onkoloji Dergisi. 2020; 30(2): 63 - 71. 10.4999/uhod.204139
IEEE EMRENCE Z,Sariman M,ABACI N,Cinar S,Salman Yaylaz B,Biberoğlu N,Cakiris A,Deniz G,Sırma Ekmekci S "The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells." Uluslararası Hematoloji-Onkoloji Dergisi, 30, ss.63 - 71, 2020. 10.4999/uhod.204139
ISNAD EMRENCE, ZELIHA vd. "The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells". Uluslararası Hematoloji-Onkoloji Dergisi 30/2 (2020), 63-71. https://doi.org/10.4999/uhod.204139