Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Cancer Rep (Hoboken). 2023 Jun;6(6):e1816. doi: 10.1002/cnr2.1816. Epub 2023 May 11.
multidrug resistance (MDR) is One of the foremost challenges in overcoming breast cancer. Various molecular processes are involved in the development of MDR in breast cancer cells, including over expression of ABC transporters such as ABCG2 (BCRP), increase breast cancer stem cells drug resistance, and epithelial mesenchymal transition.
In the present study, we used bioinformatics and experimental analysis to investigate the role of miR-548 K, in the modulating of ABCG2, in MDR breast cancer cells.
In silico inspections introduce 14 microRNAs targeting 3'-UTR region of ABCG2 transcripts, which are probably involved in breast cancer drug resistance. An association was highlighted between miR-548 k with ABC transporter family. The expression level of ABCG2 gene in MCF7-MX cell lines was significantly more than MCF7 cell lines. On the other hand, we increased the expression of miR-548 K in MCF7-MX and MCF7 cell lines through its transfection, which dramatically coincided with decreasion in the ABCG2 transcripts level. Additional studies on patient samples revealed that the expression of ABCG2 showed an increase in ABCG2 level in neoadjuvant chemotherapy drugs resistance (NCDR) patients compared to primary pre-operative chemotherapy drugs response (PCDR) patients. Also, a reduction in the expression of miR-548 K in NCDR patients was revealed.
The results of our study suggest that miR-548 K may be involved in modulating the expression of ABCG2 in MDR breast cancer cells.
多药耐药(MDR)是克服乳腺癌的首要挑战之一。多种分子过程参与了乳腺癌细胞中 MDR 的发展,包括 ABC 转运蛋白的过度表达,如 ABCG2(BCRP),增加乳腺癌干细胞的耐药性,以及上皮间质转化。
本研究通过生物信息学和实验分析,探讨 miR-548K 在调节 ABCG2 介导的 MDR 乳腺癌细胞中的作用。
计算机检索确定了 14 个可能参与乳腺癌耐药的靶向 ABCG2 转录本 3'-UTR 区域的 microRNAs。miR-548K 与 ABC 转运蛋白家族之间存在关联。MCF7-MX 细胞系中 ABCG2 基因的表达水平明显高于 MCF7 细胞系。另一方面,我们通过转染增加了 MCF7-MX 和 MCF7 细胞系中 miR-548K 的表达,这与 ABCG2 转录本水平的显著下降相一致。对患者样本的进一步研究表明,与原发性术前化疗药物反应(PCDR)患者相比,新辅助化疗药物耐药(NCDR)患者中 ABCG2 的表达增加,NCDR 患者中 miR-548K 的表达降低。
本研究结果提示,miR-548K 可能参与调节 MDR 乳腺癌细胞中 ABCG2 的表达。