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.

miR‑218 functions as a tumor suppressor gene in cervical cancer

“…GO term analysis revealed that ROBO1was involved in cell proliferation, adhesion and migration, and cell cycle regulation. Previous studies have also reported that ROBO1 is a target of miR-218 in certain types of cancer, such as hepatocellular carcinoma, glioma and nasopharyngeal cancer (21,46,47); however, the present study only predicted and confirmed it as a target gene of miR-218 in cervical cancer cells via RT-qPCR analysis. Therefore, future studies are required to investigate the regulation of ROBO1 by miR-218 and the downstream gene pathways.…”

Systematic analyses of a novel lncRNA‐associated signature as the prognostic biomarker for Hepatocellular Carcinoma

“…The large‐scale genome analyses have revealed the molecular characteristics associated with HCC OS . However, most studies focused on miRNA, mRNA, gene, and protein expression . With knowledge growing, the functional role of lncRNAs in tumorigenesis and development also represents a significant untapped resource for HCC prognosis.…”

“…[23][24][25] However, most studies focused on miRNA, mRNA, gene, and protein expression. [26][27][28][29][30] T A B L E 3 (Continued) growing, the functional role of lncRNAs in tumorigenesis and development also represents a significant untapped resource for HCC prognosis.…”

Human circular RNA‑0054633 regulates high glucose‑induced vascular endothelial cell dysfunction through the microRNA‑218/roundabout 1 and microRNA‑218/heme oxygenase‑1 axes

“…In addition, several studies have demonstrated that ROBO1 functions as a promoter of cell proliferation (19). It has also been observed that the expression of miR-218 has an inhibitory effect on cell proliferation and metastasis (19,20). These previous findings suggested that the expression of miR-218 suppressed cell proliferation and metastasis by targeting ROBO1.…”

“…ROBO1, also known as protein SAX3, is the receptor of slit guidance ligand 1 (SLIT1) and SLIT2, which are associated with cell migration. In addition, several studies have demonstrated that ROBO1 functions as a promoter of cell proliferation (19). It has also been observed that the expression of miR-218 has an inhibitory effect on cell proliferation and metastasis (19,20).…”