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Constructing a circRNA-miRNA-mRNA Network and Identifying Potential Therapeutic Agents for Breast Cancer

43 Pages Posted: 27 Apr 2019

See all articles by Si Yang

Si Yang

Zhejiang University - Department of Breast Surgery; Xi'an Jiaotong University (XJTU) - Department of Oncology

Yanshen Hou

Xinjiang Medical University

Meng Wang

Xi'an Jiaotong University (XJTU) - Department of Oncology

Yujiao Deng

Zhejiang University - Department of Breast Surgery; Xi'an Jiaotong University (XJTU) - Department of Oncology

Ying Wu

Xi'an Jiaotong University (XJTU) - Department of Oncology

Peng Xu

Xi'an Jiaotong University (XJTU) - Department of Oncology

Na Li

Zhejiang University - Department of Breast Surgery; Xi'an Jiaotong University (XJTU) - Department of Oncology

Tian Tian

Xi'an Jiaotong University (XJTU) - Department of Oncology

Linghui Zhou

Xi'an Jiaotong University (XJTU) - Department of Oncology

Qian Hao

Xi'an Jiaotong University (XJTU) - Department of Oncology

Zhen Zhai

Xi'an Jiaotong University (XJTU) - Department of Oncology

Dai Zhang

Xi'an Jiaotong University (XJTU) - Department of Oncology

Huafeng Kang

Xi'an Jiaotong University (XJTU) - Department of Oncology

Zhi-Jun Dai

Zhejiang University - Department of Breast Surgery; Xi'an Jiaotong University (XJTU) - Department of Oncology

More...

Abstract

Background: Circular RNAs (circRNAs) are central regulators for tumour progression. However, their effects are not entirely definitive in breast cancer (BRCA). We determined the potential function and regulation mechanisms of novel circRNAs in BRCA.

Methods: Bioinformatics analyses were used to identify novel circRNAs related to BRCA and to construct circRNA -miRNA-mRNA regulatory network.

Findings: Seven differentially expressed circRNAs (DECs) were identified from a microarray dataset (GSE101123). miRNA-binding sites of the seven circRNAs were forecasted. Seventeen circRNA-miRNA interactions were identified, including six circRNAs and 15 miRNAs; 2355 miRNA-related target genes and 1608 differentially expressed genes (DEGs) in BRCA were gathered. There were 149 overlapping genes between the set of miRNA target genes and the set of DEGs. A protein-protein interaction (PPI) network was constructed, which was based on the 149 genes. From this PPI network, seven hub genes are determined. The 149 genes were found to connect with several biological processes and pathways related to tumour. Based on these genes, three compounds (proadifen, pyrimethamine, and arachidonic acid) were identified as therapeutic options for BRCA through connectivity map (CMap) analysis. A circRNA-mediated network was constructed in this study.

Interpretation: Our understanding of circRNAs helps to further determine the molecular mechanisms of BRCA and to provide new treatment options.

Funding: This study was supported by National Natural Science Foundation of China (No. 81471670); the International Cooperative Project of Shaanxi province, China (No. 2016KW-008) and the Key research and development plan, Shaanxi Province, China (2017ZDXM-SF-066).

Declaration of Interest: The authors declare that they have no competing financial interests.

Suggested Citation

Yang, Si and Hou, Yanshen and Wang, Meng and Deng, Yujiao and Wu, Ying and Xu, Peng and Li, Na and Tian, Tian and Zhou, Linghui and Hao, Qian and Zhai, Zhen and Zhang, Dai and Kang, Huafeng and Dai, Zhi-Jun, Constructing a circRNA-miRNA-mRNA Network and Identifying Potential Therapeutic Agents for Breast Cancer (April 23, 2019). Available at SSRN: https://ssrn.com/abstract=3377511

Si Yang

Zhejiang University - Department of Breast Surgery

Hangzhou
China

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Yanshen Hou

Xinjiang Medical University

393 Xinyi Rd, Xinshi Qu
Wulumuqi Shi
Xinjiang Weiwuerzizhiqu, 830011
China

Meng Wang

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Yujiao Deng

Zhejiang University - Department of Breast Surgery

Hangzhou
China

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Ying Wu

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Peng Xu

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Na Li

Zhejiang University - Department of Breast Surgery

Hangzhou
China

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Tian Tian

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Linghui Zhou

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Qian Hao

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Zhen Zhai

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Dai Zhang

Xi'an Jiaotong University (XJTU) - Department of Oncology

Xi'an
China

Huafeng Kang

Xi'an Jiaotong University (XJTU) - Department of Oncology ( email )

Xi'an
China

Zhi-Jun Dai (Contact Author)

Zhejiang University - Department of Breast Surgery ( email )

Hangzhou
China

Xi'an Jiaotong University (XJTU) - Department of Oncology ( email )

Xi'an
China

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