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

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.

SUBMITTER: Wang J

PROVIDER: S-EPMC5617426 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Wang Junqing J Zhou Yunyun Y Fei Xiaochun X Chen Xunhua X Chen Rui R Zhu Zhenggang Z Chen Yongjun Y

Oncotarget 20170523 37

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 throug ...[more]

PMID: 28977866

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Project description:Integrative Bioinformatics analysis helps to explore various mechanisms of Nitroglycerin activity in different types of cancers and help predict target genes through which Nitroglycerin affect cancers. Many publicly available databases and tools were used for our study. First step in this study is identification of Interconnected Genes. Using Pubchem and SwissTargetPrediction Direct Target Genes (activator, inhibitor, agonist and suppressor) of Nitroglycerin were identified. PPI network was constructed to identify different types of cancers that the 12 direct target genes affected and the Closeness Coefficient of the direct target genes so identified. Pathway analysis was performed to ascertain biomolecules functions for the direct target genes using CluePedia App. Mutation Analysis revealed Mutated Genes and types of cancers that are affected by the mutated genes. While the PPI network construction revealed the types of cancer that are affected by 12 target genes this step reveals the types of cancers affected by mutated cancers only. Only mutated genes were chosen for further study. These mutated genes were input into STRING to perform NW Analysis. NW Analysis revealed Interconnected Genes within the mutated genes as identified above. Second Step in this study is to predict and identify Upregulated and Downregulated genes. Data Sets for the identified cancers from the above procedure were obtained from GEO Database. DEG Analysis on the above Data sets was performed to predict Upregulated and Downregulated genes. A comparison of interconnected genes identified in step 1 with Upregulated and Downregulated genes obtained in step 2 revealed Co-Expressed Genes among Interconnected Genes. NW Analysis using STRING was performed on Co-Expressed Genes to ascertain Closeness Coefficient of Co-Expressed genes. Gene Ontology was performed on Co-Expressed Genes to ascertain their Functions. Pathway Analysis was performed on Co-Expressed Genes to identify the Types of Cancers that are influenced by co-expressed genes. The four types of cancers identified in Mutation analysis in step 1 were the same as the ones that were identified in this pathway analysis. This further corroborates the 4 types of cancers identified in Mutation analysis. Survival Analysis was done on the co-expressed genes as identified above using Survexpress. BIOMARKERS for Nitroglycerin were identified for four types of cancers through Survival Analysis. The four types of cancers are Bladder cancer, Endometrial cancer, Melanoma and Non-small cell lung cancer.

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

Publications

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

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