Department of Hematology, The First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Bengbu, 233004, Anhui, People's Republic of China.
Department of Hematology, Bengbu Medical College, No. 287 Changhuai Road, Bengbu, 233004, Anhui, People's Republic of China.
Biol Res. 2019 Mar 15;52(1):11. doi: 10.1186/s40659-019-0218-7.
The present study aimed to investigate the underlying role of interferon-regulatory factor 2 (IRF2)-inositol polyphosphate-4-phosphatase, type-II (INPP4B) axis in the regulation of autophagy in acute myeloid leukemia (AML) cells.
Quantitative real time PCR (QRT-PCR) and western blot were performed to determine the expression levels of IRF2, INPP4B and autophagy-related markers in AML cell lines. Autophagy was assessed by elevated Beclin-1 expression, the conversion of light chain 3 (LC3)-I to LC3-II, downregulated p62 expression and green fluorescent protein (GFP)-LC3 puncta formation. The colony formation and apoptosis assays were performed to determine the effects of IRF2 and INPP4B on the growth of AML cells.
IRF2 and INPP4B were highly expressed in AML cell lines, and were positively correlated with autophagy-related proteins. Overexpression of IRF2 or INPP4B stimulated autophagy of AML cells, whereas inhibition of IRF2 or INPP4B resulted in the attenuation of autophagy. More importantly, IRF2 or INPP4B overexpression reversed autophagy inhibitor, 3-methyladenine (3-MA)-induced proliferation-inhibitory and pro-apoptotic effects, while IRF2 or INPP4B silencing overturned the proliferation-promoting and anti-apoptotic effects of autophagy activator rapamycin.
IRF2-INPP4B signaling axis attenuated apoptosis through induction of autophagy in AML cells.
本研究旨在探讨干扰素调节因子 2（IRF2）-肌醇多磷酸-4-磷酸酶，II 型（INPP4B）轴在调节急性髓系白血病（AML）细胞自噬中的作用。
采用定量实时 PCR（QRT-PCR）和 Western blot 检测 AML 细胞系中 IRF2、INPP4B 和自噬相关标志物的表达水平。通过 Beclin-1 表达上调、LC3-I 向 LC3-II 的转化、p62 表达下调和绿色荧光蛋白（GFP）-LC3 斑点形成来评估自噬。通过集落形成和凋亡测定来确定 IRF2 和 INPP4B 对 AML 细胞生长的影响。
IRF2 和 INPP4B 在 AML 细胞系中高表达，与自噬相关蛋白呈正相关。IRF2 或 INPP4B 的过表达刺激 AML 细胞的自噬，而 IRF2 或 INPP4B 的抑制导致自噬减弱。更重要的是，IRF2 或 INPP4B 的过表达逆转了自噬抑制剂 3-甲基腺嘌呤（3-MA）诱导的增殖抑制和促凋亡作用，而 IRF2 或 INPP4B 的沉默则推翻了自噬激活剂雷帕霉素的促增殖和抗凋亡作用。
IRF2-INPP4B 信号轴通过诱导 AML 细胞自噬来减弱细胞凋亡。
