Determination of the key ccRCC-related molecules from monolayer network to three-layer network

Clear cell renal cell carcinoma (ccRCC), with an increasing incidence rate, is one of the ubiquitous cancers. Its pathogenic factors are complicated and the molecular mechanism is not clear. It is essential to analyze the potential key genes related to ccRCC carcinogenesis. In this study, the differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) of ccRCC were screened from TCGA database. Then the miRNA-mRNA network, lncRNA-miRNA network and lncRNA-mRNA network were constructed by online database or WGCNA algorithm. Topology attributes of these monolayer networks showed that hsa-mir-155, hsa-mir-200c, hsa-mir-122, hsa-mir-506, hsa-mir-216b, hsa-mir-141, lncRNA AC137723.1 and AC021074.3 are the crucial genes related with the regulatory effects on the proliferation, metastasis and invasion of ccRCC cells. Subsequently, these three monolayer networks were integrated into a lncRNA-miRNA-mRNA multilayer network. Considering node degree, closeness centrality and betweenness centrality, we found hsa-mir-122 is screened out as the only crucial gene in three-layer network. In order to better illustrate the effect of hsa-mir-122 on ccRCC, the lncRNA-hsa-mir-122-mRNA network was constructed with hsa-mir-122 as the center. Pathway analysis of the unique target gene GALNT3 linked to hsa-mir-122 showed that GALNT3 influenced the metabolic process of mucin type O-Glycan biosynthesis. LncRNA AC090377.1 is the unique gene that has target genes among lncRNAs with clinical significance that linked to hsa-mir-122 in the lncRNA-hsa-mir-122-mRNA network. Pathway analysis of AC090377.1 suggested that GUCY2F enriched in phototransduction pathway associated with retina. From monolayer network to three-layer network, hsa-mir-122 is identified as an important molecule in the oncogenesis and progression of ccRCC, offering new strategies to further study of the carcinogenic mechanism of ccRCC.