Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145

PeerJ

article

Sili Long¹  Danwei Ren¹  Fangfang Zhong¹  Yana Niu¹  Xiang Qin¹  Dan Mu¹  Wenjun Liu¹ 

[1] Department of Pediatrics, Affiliated Hospital of Southwest Medical University, Children’s Blood and Tumor PI laboratory, Birth Defects Clinical Medical Research Center of Sichuan Province

关键词: Acute lymphoblastic leukemia;    miR-145;    Children;    Glucocorticoid;    Drug resistance;   

DOI  :  10.7717/peerj.9337

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Objective To analyze the expression levels of miR-145 in ALL children and their effects on the prognosis of ALL and to explore the mechanism of miR-145 in reversing the resistance of ALL cells to glucocorticoids. Methods A GEO database dataset was used to analyze the expression levels of miR-145 in ALL children. The association between miR-145 and childhood prognosis was analyzed by the TARGET database data. The expression levels of miR-145 in the glucocorticoid-resistant ALL cell line CEM-C1 were increased by lipofectamine 2000-mediated transfection. Cell proliferation inhibition experiments were performed to detect the effect of miR-145 on the response of CEM-C1 cell line to glucocorticoids. The expression levels of the apoptotic, autophagic and drug resistance-associated genes and proteins were detected by qPCR and western blot analysis. Results The expression levels of miR-145 were decreased in ALL patients (P < 0.001) and the prognosis of ALL in children with high miR-145 expression was significantly improved (P < 0.001). Increased miR-145 expression can improve the sensitivity of CEM-C1 cells to glucocorticoids. The expression levels of the proapoptotic and the anti-apoptotic genes Bax and Bcl-2 were increased and decreased, respectively, whereas the expression levels of the autophagicgenes Beclin 1 and LC were increased. In addition, the expression levels of the drug resistance gene MDR1 were decreased. Conclusion The expression levels of miR-145 in ALL children were decreased and they were associated with disease prognosis. The data indicated that miR-145 can reverse cell resistance by regulating apoptosis of CEM-C1 cells and autophagy.

【 授权许可】

CC BY