机构：[1]Department of Surgical Nursing, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050017, PR China[2]Research Center, the Fourth Hospital of Hebei Medical University/Tumor Research Institute of Hebei Province, Shijiazhuang, Hebei, 050017, PR China河北医科大学第四医院[3]Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei, 050017, PR China
Background: Circular RNAs (circRNAs) have attracted lots of attention in tumorigenesis and progression. However, circRNAs as crucial regulators in epithelial-mesenchymal transition have not been systematically identified in breast cancer. The purpose of our research was to investigate the circRNA network associated with epithelial-mesenchymal transition in breast cancer. Methods: Expression profiling data of circRNAs were identified by circRNA microarray in transfected ZEB1 and control breast cancer cells. The differentially expressed circRNAs, miRNAs, and mRNAs were determined via fold change filtering. The competing endogenous RNAs (ceRNAs) network was established on the foundation of the relationship between circular RNAs, miRNAs and mRNAs. The CytoHubba was used to determine the hub genes from the protein-protein interaction (PPI) regulatory network. The GEPIA database was used to observe the expression of the hub genes mRNA between breast cancer tissues and normal tissues. The HPA database was applied to investigate the expression of six hub genes at the protein level. Morever, we further used Kaplan-Meier plotter to perform survival analysis of these hub genes. Results: The top three up-regulated differential expressed circRNAs were identified by circRNA microarray. Following the Real-time PCR validation of the three circRNAs, two circRNAs (hsa_circRNA_002082 and hsa_circRNA_400031) were selected for further analysis. After the predicted target miRNA, ten circRNA-miRNA interactions including two circRNAs and ten miRNAs were determined. Furthermore, the Venn diagram was used to intersect the predicted target genes and the differentially expressed genes, and screened 174 overlapped genes. Subsequently, we constructed a PPI network, and selecting six hub genes, containing KIF4A, CENPF, OIP5, ZWINT, DEPDC1, BUB1B. The mRNA expression levels of the six hub genes were obviously up-regulated in breast cancer. The protein expression levels of KIF4A, CENPF, OIP5, and DEPDC1 were significantly increased in breast cancer tissues. Moreover, the survival analysis results revealed that high expression of the six hub genes were obviously correlated with poor prognosis of breast cancer patients. Conclusions: Our study constructed and analyzed a circRNA-associated ceRNA regulatory network and discovered that hsa_circRNA_002082 and hsa_circRNA_400031 may mechanism as ceRNAs to serve key roles in breast cancer epithelial-mesenchymal transition.
基金：
This work was supported by Hebei Provincial Health Department
[20190088, 20201209] and Hebei Provincial Administration of
Traditional Chinese Medicine [2019133].
第一作者机构：[1]Department of Surgical Nursing, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050017, PR China[2]Research Center, the Fourth Hospital of Hebei Medical University/Tumor Research Institute of Hebei Province, Shijiazhuang, Hebei, 050017, PR China
共同第一作者：
通讯作者：
通讯机构：[2]Research Center, the Fourth Hospital of Hebei Medical University/Tumor Research Institute of Hebei Province, Shijiazhuang, Hebei, 050017, PR China[*1]Research Center, the Fourth Hospital of Hebei Medical University, No. 12 jiankang Road, Shijiazhuang, Hebei, 050017, PR China.
推荐引用方式(GB/T 7714)：
Sang Meijie,Wu Ming,Meng Lingjiao,et al.Identification of epithelial-mesenchymal transition-related circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer[J].PATHOLOGY RESEARCH AND PRACTICE.2020,216(9):doi:10.1016/j.prp.2020.153088.
APA：
Sang, Meijie,Wu, Ming,Meng, Lingjiao,Zheng, Yang,Gu, Lina...&Sang, Meixiang.(2020).Identification of epithelial-mesenchymal transition-related circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer.PATHOLOGY RESEARCH AND PRACTICE,216,(9)
MLA：
Sang, Meijie,et al."Identification of epithelial-mesenchymal transition-related circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer".PATHOLOGY RESEARCH AND PRACTICE 216..9(2020)
