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微小RNA-3163介导的ABCG2沉默抑制视网膜母细胞瘤癌干细胞的多药耐药性

Silencing of ABCG2 by MicroRNA-3163 Inhibits Multidrug Resistance in Retinoblastoma Cancer Stem Cells.

作者信息

Jia Ming, Wei Zhenhua, Liu Peng, Zhao Xiaoli

机构信息

Department of Ophthalmology, Linzi District People's Hospital, Zibo City, Shandong Province, P. R. China .

出版信息

J Korean Med Sci. 2016 Jun;31(6):836-42. doi: 10.3346/jkms.2016.31.6.836. Epub 2016 Apr 20.

Abstract

To investigate the function and regulation mechanism of ATP-binding cassette, subfamily G, member 2 (ABCG2) in retinoblastoma cancer stem cells (RCSCs), a long-term culture of RCSCs from WERI-Rb1 cell line was successfully established based on the high expression level of ABCG2 on the surface of RCSCs. To further explore the molecular mechanism of ABCG2 on RCSCs, a microRNA that specifically targets ABCG2 was predicted. Subsequently, miR-3163 was selected and confirmed as the ABCG2-regulating microRNA. Overexpression of miR-3163 led to a significant decrease in ABCG2 expression. Additionally, ABCG2 loss-of-function induced anti-proliferation and apoptosis-promoting functions in RCSCs, and multidrug resistance to cisplatin, carboplatin, vincristine, doxorubicin, and etoposide was greatly improved in these cells. Our data suggest that miR-3163 has a significant impact on ABCG2 expression and can influence proliferation, apoptosis, and drug resistance in RCSCs. This work may provide new therapeutic targets for retinoblastoma.

摘要

为了研究ATP结合盒亚家族G成员2(ABCG2)在视网膜母细胞瘤癌干细胞(RCSCs)中的功能及调控机制,基于RCSCs表面ABCG2的高表达水平,成功建立了来自WERI-Rb1细胞系的RCSCs长期培养体系。为进一步探究ABCG2对RCSCs的分子机制,预测了一种特异性靶向ABCG2的微小RNA。随后,选择并确认miR-3163为调控ABCG2的微小RNA。miR-3163的过表达导致ABCG2表达显著降低。此外,ABCG2功能缺失诱导RCSCs的抗增殖和促凋亡功能,并且这些细胞对顺铂、卡铂、长春新碱、阿霉素和依托泊苷耐药性大大提高。我们的数据表明,miR-3163对ABCG2表达有显著影响,并可影响RCSCs的增殖、凋亡和耐药性。这项工作可能为视网膜母细胞瘤提供新的治疗靶点。

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