Jia Ming, Wei Zhenhua, Liu Peng, Zhao Xiaoli
Department of Ophthalmology, Linzi District People's Hospital, Zibo City, Shandong Province, P. R. China .
J Korean Med Sci. 2016 Jun;31(6):836-42. doi: 10.3346/jkms.2016.31.6.836. Epub 2016 Apr 20.
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.
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。