Mohammadi Yeganeh S, Vasei M, Tavakoli R, Kia V, Paryan M
Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Eur J Cancer Care (Engl). 2017 Nov;26(6). doi: 10.1111/ecc.12496. Epub 2016 May 27.
Breast cancer is a heterogeneous disease, and among all types, triple-negative breast cancer (TNBC) is characterised by high risk of recurrence. The discovery of microRNAs (miRNA) has opened the door for targeted therapy of TNBC. miR-340 down-regulation and sub-G1-accumulated cells in flowcytometry were observed in metastatic TNBC cells (data in publication), leading us to investigate the potential tumour suppressive role of this miRNA on cell-cycle-related genes. A lentiviral vector containing miR-340 was applied to over-express miR-340 in TNBC cell line, MDA-MB-231. Then, the expression of some cell-cycle-regulating genes including cyclin A2 (cyclin A2), Cyclin-dependent kinases 2 (CDK2), cyclin-dependent kinase inhibitors (P16, P18 and P27), Retinoblastoma (RB) and transcription factors (SMAD 4, SOX2 and SOX17) was investigated using quantitative RT-PCR. The results showed a decline in the expression of SOX2, P16 and P27 after miR-340 over-expression, whereas we observed an increase in the expression of cyclin A2, CDK2, SOX17, P18, SMAD 4 and RB. The over-expression of tumour suppressor genes such as RB and SOX17 and down-regulation of an oncogene such as SOX2 were in accordance to the inhibitory role of miR-340 that causes blockage of breast cancer metastasis which should be further investigated.
乳腺癌是一种异质性疾病,在所有类型中,三阴性乳腺癌(TNBC)的特点是复发风险高。微小RNA(miRNA)的发现为TNBC的靶向治疗打开了大门。在转移性TNBC细胞中观察到miR-340下调以及流式细胞术中亚G1期细胞积累(发表数据),这促使我们研究这种miRNA对细胞周期相关基因的潜在肿瘤抑制作用。将含有miR-340的慢病毒载体应用于TNBC细胞系MDA-MB-231中以过表达miR-340。然后,使用定量RT-PCR研究了一些细胞周期调节基因的表达,包括细胞周期蛋白A2(cyclin A2)、细胞周期蛋白依赖性激酶2(CDK2)、细胞周期蛋白依赖性激酶抑制剂(P16、P18和P27)、视网膜母细胞瘤(RB)和转录因子(SMAD 4、SOX2和SOX17)。结果显示,miR-340过表达后,SOX2、P16和P27的表达下降,而我们观察到细胞周期蛋白A2、CDK2、SOX17、P18、SMAD 4和RB的表达增加。肿瘤抑制基因如RB和SOX17的过表达以及癌基因如SOX2的下调与miR-340的抑制作用一致,miR-340可导致乳腺癌转移受阻,对此应进一步研究。