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

被引:9
作者
Wang, Junqing [1 ,2 ,3 ]
Zhou, Yunyun [4 ]
Fei, Xiaochun [5 ]
Chen, Xunhua [2 ,3 ]
Chen, Rui [6 ]
Zhu, Zhenggang [1 ,2 ,3 ]
Chen, Yongjun [1 ]
机构
[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Surg, Sch Med, Shanghai 20025, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Inst Digest Surg, Ruijin Hosp, Sch Med, Shanghai 20025, Peoples R China
[3] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Key Lab Gastr Neoplasms, Sch Med, Shanghai 20025, Peoples R China
[4] Univ Mississippi, Med Ctr, Dept Data Sci, Jackson, MS 39216 USA
[5] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Pathol, Sch Med, Shanghai 20025, Peoples R China
[6] Shanghai Jiao Tong Univ, Renji Hosp, Dept Plast & Reconstruct Surg, Sch Med, Shanghai 200001, Peoples R China
基金
中国国家自然科学基金;
关键词
hepatocellular carcinoma; bioinformatics analysis; ROBO1; MiR-218; CELL-PROLIFERATION; GASTRIC-CANCER; GENES; EXPRESSION; PROMOTES; ANGIOGENESIS; MICRORNA-218; METASTASIS; INVASION; PATHWAY;
D O I
10.18632/oncotarget.18099
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:61327 / 61337
页数:11
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