High expression of microRNA-183/182/96 cluster as a prognostic biomarker for breast cancer.

Cailu Song,Zhongying Huang,Hailin Tang,Xiaoming Xie,Jin Wang,Mingqing Wu,Shuaijie Li,Lijuan Zhang,Xing Li

doi:10.1038/srep24502

Cailu Song, Zhongying Huang + Show 7 more

Open Access

https://doi.org/10.1038/srep24502

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Abstract

More sensitive and effective diagnostic markers for the detection of breast cancer are urgently needed. The microRNA-183/182/96 cluster has been reported to be involved in tumorigenesis and progression in a variety of cancers, and it is a promising cancer prognostic biomarker. The goal of this study was to determine the expression levels of the miR-183/182/96 cluster in breast cancer tissues and evaluate its prognostic role in breast cancer. Real-time quantitative polymerase chain reaction analysis (qRT-PCR) was used to detect the expression levels of the miR-183/182/96 cluster in 41 breast cancer tissues and adjacent normal tissues (control tissues) and also in different mammary cell lines. In situ hybridization (ISH) of the miR-183/182/96 cluster on 131 tissue microarrays (TMAs) was used to statistically analyze its prognostic role. The miR-183/182/96 cluster levels were significantly higher in breast cancer tissues than in control tissues. The miR-183/182/96 cluster was also upregulated in human breast cancer cell lines. An increased miR-183/182/96 cluster level was correlated with local relapse, distant metastasis and poor clinical outcomes. Our findings improve our understanding of the expression level of the miR-183/182/96 cluster in breast cancer and clarify the role of the miR-183/182/96 cluster as a novel prognostic biomarker for breast cancer.

Highlights

Breast cancer is the most common malignancy and the main cause of death among women
QRT-PCR analysis was used to detect the expression of miR-183/182/96 in 12 different mammary cell lines, including human breast cancer cell lines (MDA-MB-435, MDA-MB-361, MDA-MB-231, BT-483, BT-474, BT-20, MCF-7, MDA-MB-468 and T-47D) and human mammary epithelial (HME) cell lines (BHL-100, 184A and MCF10A)
We found that miR-183/182/96 was upregulated in human breast cancer cell lines compared to in HME cell lines (Fig. 1A)

Summary

Introduction

Breast cancer is the most common malignancy and the main cause of death among women. A total of 232, 340 new cases of invasive breast cancer and 39, 620 breast cancer deaths were expected to occur among US women in 20131. MiRNAs are single-stranded RNA molecules of approximately 22 nucleotides in length These small regulatory RNA molecules can modulate the activity of specific mRNA targets by pairing to the messenger RNAs (mRNAs) of protein-coding genes. MiRNAs exert posttranscriptional repression functions by binding to complementary sequences in the 3′ -untranslated regions (3′ -UTR) of mRNAs to promote mRNA degradation or block translation[8] They play an important role in a wide range of physiologic and pathologic processes in animals and plants. In most types of breast cancers, overexpression of the miR-183/182/96 cluster has been reported to increase cell proliferation and migration. It is well known that the expression level of the miR-183/182/96 cluster is increased in several tumor types, its prognostic role in breast cancer is still unclear. We evaluated the OS and DFS of breast cancer patients with high and low expression of the miR-183/182/96 cluster to further judge its prognostic role for breast cancer

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