Rath Sandip Kumar, Deb Moonmoon, Sengupta Dipta, Kari Vijayalaxmi, Kar Swayamsiddha, Parbin Sabnam, Pradhan Nibedita, Patra Samir Kumar
Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.
Cell Signalling Group, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Tumour Biol. 2016 Sep;37(9):12535-12546. doi: 10.1007/s13277-016-5114-y. Epub 2016 Jun 27.
The role and clinical implication of ZRF1 in breast cancer are poorly understood. So this study is aimed to explore the role of ZRF1 in breast cancer progression. With this context, we first assessed its expression pattern in FFPE primary and metastasis breast tissue samples as well as from publicly available databases. Moreover, we also explored the survival status of patients from the publicly available database and interestingly discover that high expression of ZRF1 decreases the survival of estrogen-positive breast cancer patients more than estrogen-negative status patients. In the perspective of this, we evaluated the role ZRF1 in MCF-7 breast cancer cells and found that it's silencing by knockdown results in decreased cell proliferation as well as cell viability. Results also show that expression of ZRF1 is down regulated in the presence of estrogen-depleted conditions but independent of RAS/MEK as well as AKT axes. Moreover, the decrease in viability of MCF-7 cells was accompanied by induction of apoptosis and DNA damage, well-marked with upregulation of cleaved PARP and downregulation of BCL2 and H2AUbK119 levels. Furthermore, we also explored that knockdown of ZRF1 sensitises the effect of curcumin, observed with decrease in cell viability and dropping of IC50 value from 25 to 15 μM. This investigation thus shed a new light on the role on ZRF1 in breast cancer cells and hence can be exploited to design better therapeutic intervention.
ZRF1在乳腺癌中的作用及临床意义尚不清楚。因此，本研究旨在探讨ZRF1在乳腺癌进展中的作用。在此背景下，我们首先评估了其在FFPE原发性和转移性乳腺组织样本以及公开数据库中的表达模式。此外，我们还从公开数据库中探究了患者的生存状况，有趣的是发现ZRF1的高表达对雌激素阳性乳腺癌患者生存率的降低作用比对雌激素阴性患者更明显。据此，我们评估了ZRF1在MCF-7乳腺癌细胞中的作用，发现通过敲低使其沉默会导致细胞增殖及细胞活力下降。结果还表明，在雌激素缺乏条件下ZRF1的表达下调，但与RAS/MEK以及AKT信号轴无关。此外，MCF-7细胞活力的降低伴随着凋亡和DNA损伤的诱导，表现为裂解的PARP上调以及BCL2和H2AUbK119水平下调。此外，我们还发现敲低ZRF1会增强姜黄素的作用，表现为细胞活力下降以及IC50值从25 μM降至15 μM。因此，本研究为ZRF1在乳腺癌细胞中的作用提供了新的见解，从而可用于设计更好的治疗干预措施。
