Oncotarget

Research Papers:

Integrative bioinformatics analysis identifies ROBO1 as a potential therapeutic target modified by miR-218 in hepatocellular carcinoma

Junqing Wang, Yunyun Zhou, Xiaochun Fei, Xunhua Chen, Rui Chen, Zhenggang Zhu and Yongjun Chen _

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Oncotarget. 2017; 8:61327-61337. https://doi.org/10.18632/oncotarget.18099

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Abstract

Junqing Wang1,2,3,*, Yunyun Zhou4,*, Xiaochun Fei5, Xunhua Chen2,3, Rui Chen6, Zhenggang Zhu1,2,3 and Yongjun Chen1

1Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 20025, People’s Republic of China

2Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 20025, People’s Republic of China

3Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 20025, People’s Republic of China

4Department of Data Science, University of Mississippi Medical Center, Jackson, MS 39216, USA

5Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 20025, People’s Republic of China

6Department of Plastic and Reconstructive Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Yongjun Chen, email: cyj10651@rjh.com.cn

Junqing Wang, email: wangjunqingmd@hotmail.com

Keywords: hepatocellular carcinoma, bioinformatics analysis, ROBO1, MiR-218

Received: March 03, 2017     Accepted: April 11, 2017     Published: May 23, 2017

ABSTRACT

Patients diagnosed with advanced hepatocellular carcinoma (HCC) presented poor prognosis and short survival time. Althouth accumulating contribution of continuous research has gradually revealed complex tumorigenesis mechanism of HCC with numerous and jumbled biomarkers, those specific ones for HCC diagnose and therapeutic treatment are required illustration. Multiple genes over-expressed in HCC specimens with at least 1.5 fold change were cohorted, compared with the non-cancerous tissues through integrative bioinformatics analysis from Gene Expression Omnibus (GEO) datasets GSE14520 and GSE6764, including 445 and 45 cases of samples spearatly, along with intensive exploration on the Cancer Genome Altas (TCGA) dataset of liver cancer. Thirteen genes significantly highly expressed, overlapping in the datasets above. The Database for Annotation Visualization and Integrated Discovery (DAVID) program was utilized for functional pathway enrichment analysis. Protein-protein Interaction (PPI) analysis was conducted through the Search Tool for the Retrieval of Interacting Genes (STRING) database. ROBO1 was highlighted as one of the most probable molecules among the 13 candidates participating in cancer process. Cancer Cell Line Encycolopedia (CCLE) database was utilized exploring ROBO1 expression in cell lines. Immunochemistry analysis and qRT-PCR assay were performed in our medical center, which indicates significant over-expression status in either HCC tumor specimens and 3 HCC cell lines. Furtherly, we recognized that miR-218, a tumor suppressor, might be an upstream regulator for ROBO1 directly binding to the mRNA 3’UTR and potentially modifying the expression and function of ROBO1. Herein, we conclude that ROBO1 is a mighty therapeutic targets modified by miR-218 in HCC deserving further investigation.


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