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Circular RNA hsa_circ_0052112 promotes cell migration and invasion by acting as sponge for miR-125a-5p in breast cancer - 20/09/18

Doi : 10.1016/j.biopha.2018.08.030 
He-da Zhang a, b, Lin-hong Jiang c, Jun-chen Hou d, Shan-liang Zhong e, Si-ying Zhou d, Ling-ping Zhu d, Jian Li f, Dan-dan Wang d, Da-wei Sun f, Zhen-ling Ji a, b, , 1 , Jin-hai Tang d,
a Department of General Surgery, School of Medicine, Southeast University, Nanjing, Jiangsu, China 
b Department of General Surgery, Institute for Minimally Invasive Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China 
c Department of Oncology, Xuzhou Medical University, Xuzhou, Jiangsu, China 
d Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China 
e Center of Clinical Laboratory, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China 
f Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China 

Corresponding author at: Department of General Surgery, Institute for Minimally Invasive Surgery, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China.Department of General SurgeryInstitute for Minimally Invasive SurgeryZhongda HospitalSchool of MedicineSoutheast University87 Ding Jia QiaoNanjingJiangsu210009China⁎⁎Corresponding author at: Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.Department of General SurgeryThe First Affiliated Hospital with Nanjing Medical University300 Guangzhou RoadNanjing210029China

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Highlights

Hsa_circ_0052112 expression is significantly dysregulated in MDAMB-231 cells.
Hsa_circ_0052112 mediates breast cancer cells migration and invasion.
Hsa_circ_0052112/ miRNA/mRNA network is established.
Hsa_circ_0052112 positively regulates its host gene, ZNF83.

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Abstract

Objectives

Accumulating evidence has been reported that circular RNAs (circRNAs) are a class of relatively stable, non-coding RNAs, which are involved in the progression of many types of diseases. However, the mechanism of hsa_circ_0052112 in breast cancer cells is not entirely clear. Hsa_circ_0052112, generated from the ZNF83 gene, is selected by analyzing circRNA expression profiles of breast cancer cell by using microarray assay. In this study, we will show the role of hsa_circ_0052112 in regulating cell invasion and migration in breast cancer.

Methods

The expression level of hsa_circ_0052112 in MCF-7 and MDA-MB-231 cells was detected by RT-qPCR; we performed transwell assay to evaluate breast cancer cells’ migration and invasion; predicated circRNA/miRNAs interaction using the miRanda and RNAhybrid software; identified the relationship between hsa_circ_0052112 and miR-125a-5p by luciferase activity assay and show the localization of hsa_circ_0052112 by FISH assay and show the significance of ZNF83 in clinical prognosis by Kaplan-Meier survival analysis.

Results

Hsa_circ_0052112 expression was significantly higher in MDA-MB-231 cells than that in MCF-7 cells. Overexpression of hsa_circ_0052112 promoted cell migration and invasion in breast cancer. Inversely, down-regulation of hsa_circ_0052112 suppressed breast cancer cells migration and invasion. Hsa_circ_0052112 was mostly located in cytoplasm. Hsa_circ_0052112 could directly sponge to miR-125a-5p; overexpression of miR-125a-5p significantly inhibited breast cancer cells migration and invasion. However, high or low expression of miR-125a-5p was not correlated with relapse free survival (RFS) by TCGA database validation, but high expression of ZNF83 was closely correlated with poor RFS by Kaplan–Meier plotter.

Conclusions

These data suggest that hsa_circ_0052112 may be a potent biomarker for breast cancer, and may provide a new perspective on treatment of breast cancer.

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Keywords : circRNAs, hsa_circ_0052112, Breast cancer, miRNA-125a-5p


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Vol 107

P. 1342-1353 - novembre 2018 Regresar al número
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