LINC03052/ hsa-miR-361-5p/ CLEC1B CeRNA axis can be involved in the HCC by mediating in C-type lectin receptor signaling pathway
LINC03052/ hsa-miR-361-5p/ CLEC1B CeRNA axis can be involved in the HCC by mediating in C-type lectin receptor signaling pathway
Hediyeh Khashei,1Mohammad Rezaei,2Mansoureh 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 one of the most common tumors in the world, with a high mortality rate and poor treatment outcomes due to an unclear molecular foundation. It appears that gene expression is important in the pathogenesis of the disease. Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene expression in many malignancies by interacting with microRNAs (miRNAs). However, the potential pathogenic functions of the ceRNA network in HCC pathogenesis are unknown. This study has employed bioinformatics analysis to detect novel biomarkers for prognostic and diagnostic targets.
Methods: We used DEGs (Differentially expressed genes) between cirrhotic Non-malignant liver tissue and tumor tissue to analyze gene expression profiles and find genes of importance in the development of hepatocellular carcinoma. Microarray data(GSE54236) was obtained from NCBI Gene Expression Omnibus (GEO). this data was analyzed by GEO2R and genes with significant differential expressions (logFC <-3 and adjusted p-value <0.05) were selected. The miRWalk was used to analyze miRNA–mRNA interactions. To find proper lncRNAs, miRNAs were searched in LncBase v.3 and several lncRNAs were found. For more, to confirm that the lncRNAs are highly significant in hepatocellular carcinoma, the lnCAR database was employed. Using GEPIA2 for validation of mRNA, and using ENCORI for validation of miRNA and lncRNA. Moreover, The Pathway enrichment analysis was carried out using KEGG.
Results: GEO2R analysis shows that CLEC1B gene to be meaningfully downregulated in Liver Hepatocellular Carcinoma (LIHC) (logFC=-3.4951, adj. P value =4.40E-12). CLEC1B gene was validated by the GEPIA2 database. Analysis of probable mRNA-miRNA interaction by miRwalk and ENCORI showed that hsa-miR-361-5p has significant interaction with CLEC1B mRNA in the 3’ end. By entering this miRNA in Lncbase v.3 and validating the interaction in ENCORI, it was revealed that LINC03052 (lncRNA) had a significant correlation with the mRNA. Additionally, to ensure that lncRNA is a high expression in hepatocellular carcinoma, the lnCAR database was employed, and the level of expression was 2.5191. Moreover, Kyoto Encyclopedia of Genes and Genomes(Kegg) database confirmed that CLEC1B is a component of C-type lectin receptor signaling pathway which has a critical function in anti-tumor immune responses.
Conclusion: Current study reveals that, there might be a CeRNA network between CLEC1B, hsa-miR-361-5p, and LINC03052. The CeRNA network and signaling pathway increase the possibility that CLEC1B is a reliable biomarker for diagnostic and prognostic targets.