• Identification of LGALS3 /hsa-miR-1225-5p/XIST ceRNA network in HCV-associated hepatocellular carcinoma patients: Integrated high-throughput bioinformatics investigation
  • Parastoo Tabaeian,1 Mohammad Rezaei,2 Mansoureh Azadeh,3,*
    1. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    2. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    3. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran


  • Introduction: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death around the world [1]. Cirrhosis is the most important risk factor of HCC which can be developed by Hepatitis B and C. HCV is a potential risk factor for cirrhosis and liver cancer progress [1].
  • Methods: In the present study, we tried to identify a potential diagnostic mRNA, a novel miRNA and finally, a ceRNA network in hepatocellular carcinoma using bioinformatics analysis. At first, liver cancer Microarray dataset GSE14323 was obtained from a study at PubMed [2] and then, analyzed by GEO2R to find differentially expressed genes (DEGs). After selecting a significant gene from the data, it was analyzed by GEPIA2[3] and ENCORI[4] to confirm its expression rate in normal and tumor samples and investigate survival analysis to find a significant relationship between high-expressed and low-expressed groups in mortality. Through Enrichr [5] gene ontology information and biological pathway, involvement was understood. In addition, protein-protein interactions were analyzed by STRING [6] to identify probable pathways that selected mRNA can regulate indirectly. miRWALK database [7] was employed to find a novel mature miRNA which has significant interaction with the selected mRNA in the CDS region. Finally, the novel miRNA was searched in LncBase v.3 [8] to find strong interactions with lncRNAs and construct a predictive ceRNA network.
  • Results: by GEO2R analysis, LGALS3 was selected as an up-regulated gene (logFC=3.1, adj. P value=7.81e-22) in tumor samples. The significant high expression of this gene in liver cancer also was shown in GEPIA2 and ENCORI. Survival analysis showed that there is a significant positive relationship between the high expression of LGALS3 and increasing mortality (log-rank p=0.0037, HR (high) =1.7, p(HR) =0.0041). This gene encodes a protein named Galectin-3 which regulates apoptosis and innate immune system. It is also related to Ras family activation regulation pathway which has a crucial role in human cancer. MiRNA-mRNA interactions analysis showed that hsa-miR-1225-5p is a significant interactor to LGALS3 mRNA. And then, XIST was found as a LncRNA which had an interaction with hsa-miR-1225-5p according to LncBase v.3.
  • Conclusion: LGALS3 is an over-expressed gene in HCC patients and forms a predictive ceRNA network among hsa-miR-1225-5p and XIST.
  • Keywords: Hepatocellular carcinoma, LGALS3, ceRNA, integrated bioinformatics