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

Sili Long; Danwei Ren; Fangfang Zhong; Yana Niu; Xiang Qin; Dan Mu; Wenjun Liu

doi:10.7717/peerj.9337

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

PeerJ. 2020 Jun 16:8:e9337. doi: 10.7717/peerj.9337. eCollection 2020.

Authors

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

Affiliation

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, Luzhou, China.

Abstract

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.

Keywords: Acute lymphoblastic leukemia; Children; Drug resistance; Glucocorticoid; miR-145.

Grants and funding

This work was supported by the Basic Research Project of Sichuan Province (No. 2019YJ0690), the Major Science and Technology Projects in Sichuan Province (No. 2019YFS0531), and the Luzhou Science and Technology Plan Project (No. 2019-RCW-96). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.