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.

透明细胞肾细胞癌（ccRCC）的发病率越来越高，是普遍存在的癌症之一。其致病因素复杂，分子机制尚不明确。分析与 ccRCC 致癌作用相关的潜在关键基因至关重要。本研究从TCGA数据库中筛选出ccRCC差异表达的mRNAs、miRNAs和lncRNAs（DEmRNAs、DEmiRNAs和DElncRNAs）。然后通过在线数据库或WGCNA算法构建miRNA-mRNA网络、lncRNA-miRNA网络和lncRNA-mRNA网络。这些单层网络的拓扑属性表明 hsa-mir-155、hsa-mir-200c、hsa-mir-122、hsa-mir-506、hsa-mir-216b、hsa-mir-141、lncRNA AC137723.1 和 AC021074 .3是与ccRCC细胞增殖、转移和侵袭的调节作用相关的关键基因。随后，这三个单层网络被整合到一个 lncRNA-miRNA-mRNA 多层网络中。考虑节点度、接近中心性和中介中心性，我们发现 hsa-mir-122 作为三层网络中唯一的关键基因被筛选出来。为了更好地说明hsa-mir-122对ccRCC的作用，以hsa-mir-122为中心构建了lncRNA-hsa-mir-122-mRNA网络。与 hsa-mir-122 相关的独特靶基因 GALNT3 的通路分析表明，GALNT3 影响粘蛋白型 O-聚糖生物合成的代谢过程。LncRNA AC090377.1是lncRNAs中具有临床意义的靶基因的独特基因，与lncRNA-hsa-mir-122-mRNA网络中的hsa-mir-122相关联。AC090377.1 的通路分析表明 GUCY2F 富含与视网膜相关的光转导通路。