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微小RNA-218通过靶向BMI-1抑制急性早幼粒细胞白血病细胞的生长。

miR-218 inhibits acute promyelocytic leukemia cell growth by targeting BMI-1.

作者信息

Wang Yan, Sun Hai-Hong, Sui Ming-Hua, Ma Jun-Jie

机构信息

Department of Hematology, Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.

Department of Emergency Intensive Care Unit, Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.

出版信息

Oncol Lett. 2017 Dec;14(6):8078-8083. doi: 10.3892/ol.2017.7220. Epub 2017 Oct 19.

DOI:10.3892/ol.2017.7220
PMID:29344251
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5755149/
Abstract

Acute promyelocytic leukemia (APL) is a subtype of acute myelocytic leukemia. Previous studies have reported a number of functions and therapeutic roles of microRNAs (miRs) in APL, and have suggested that miR-218 acts as a tumor suppressor in a number of types of human cancer; however, its role in APL remains unclear. In the present study, the expression of miR-218 and its effects on the viability and proliferation of HL-60 cells was investigated. Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that miR-218 was frequently downregulated in APL marrow tissues compared with normal marrow tissues. Overexpression of miR-218 significantly inhibited cell proliferation, arrested the cell cycle in the G/G phase and induced apoptosis. In addition, B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) mRNA expression was negatively associated with miR-218 expression; BMI-1 mRNA and protein expression were downregulated following transfection with miR-218 mimic. These results indicate that miR-218 functions as tumor suppressor in APL, and the miR-218/BMI-1 signaling axis may be a potential novel diagnostic marker and therapeutic target for the treatment of APL.

摘要

急性早幼粒细胞白血病(APL)是急性髓细胞白血病的一种亚型。先前的研究报道了微小RNA(miR)在APL中的多种功能和治疗作用,并表明miR-218在多种人类癌症中发挥肿瘤抑制作用;然而,其在APL中的作用仍不清楚。在本研究中,研究了miR-218的表达及其对HL-60细胞活力和增殖的影响。逆转录-定量聚合酶链反应分析表明,与正常骨髓组织相比,miR-218在APL骨髓组织中经常下调。miR-218的过表达显著抑制细胞增殖,使细胞周期停滞在G/G期并诱导细胞凋亡。此外,B细胞特异性莫洛尼鼠白血病病毒整合位点1(BMI-1)mRNA表达与miR-218表达呈负相关;用miR-218模拟物转染后,BMI-1 mRNA和蛋白表达下调。这些结果表明,miR-218在APL中发挥肿瘤抑制作用,miR-218/BMI-1信号轴可能是治疗APL的潜在新型诊断标志物和治疗靶点。

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