髓系白血病
RNA结合蛋白
爆炸危机
小RNA
核糖核酸
细胞生物学
癌症研究
化学
基因
生物
生物化学
作者
Minran Zhou,Xiaolin Yin,Lu Zhang,Zelong Cui,Xinwen Jiang,Qingli Ji,Sai Ma,Chunyan Chen
标识
DOI:10.1158/1541-7786.c.7476320
摘要
<div>Abstract<p>The blast crisis (BC) of chronic myeloid leukemia (CML) has poor efficacy against existing treatments and extremely short survival. However, the molecular mechanism of CML-chronic phase (CP) transformation to CML-BC is not yet fully understood. Here, we show that Lin28B, an RNA-binding protein, acted as an activator enhancing the transformation to CML-BC by mediating excessive cell proliferation. The level of Lin28B expression was apparently elevated in patients with CML-BC compared with newly diagnosed patients with CML-CP. The overexpression of Lin28B promoted the proliferation of leukemia cells. Mechanistically, we identified Lin28B as a DNA-binding protein by binding to the promoter region of miR-181d and upregulating its expression, which inhibited the expression of programmed cell death 4 (PDCD4) by binding to the PDCD4 3'UTR region, thereby enhancing the proliferation of CML cells. Overall, the “Lin28B-miR-181d-PDCD4” regulatory axis promoted CML blast crisis.</p><p><b>Implications:</b> Our findings highlight the oncogenic role of Lin28B in CML blast crisis, acting as a DNA-binding protein that transcriptionally upregulates miR-181d expression.</p></div>
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