School of Science, Jiangnan University, Wuxi, Jiangsu 214122, PR China; Laboratory of Media Design and Software Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China.
School of Science, Jiangnan University, Wuxi, Jiangsu 214122, PR China; Key Laboratory of Industrial Biotechnology, Jiangnan University, Wuxi, Jiangsu 214122, PR China.
Cancer Genet. 2021 Aug;256-257:40-47. doi: 10.1016/j.cancergen.2021.03.005. Epub 2021 Apr 20.
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) 的发病率不断上升，是一种普遍存在的癌症。其发病因素复杂，分子机制尚不清楚。分析与 ccRCC 发生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 的差异表达 mRNA、miRNA 和 lncRNA（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、转移和侵袭的调控作用相关的关键基因。随后，将这三个单层网络整合到一个 lncRNA-miRNA-mRNA 多层网络中。考虑节点度、接近中心度和介数中心度，发现 hsa-mir-122 是从三层网络中筛选出的唯一关键基因。为了更好地说明 hsa-mir-122 对 ccRCC 的影响，以 hsa-mir-122 为中心构建了 lncRNA-hsa-mir-122-mRNA 网络。与 hsa-mir-122 相关的唯一靶基因 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。在 lncRNA-hsa-mir-122-mRNA 网络中，与 hsa-mir-122 相关的具有临床意义的 lncRNA 中唯一的靶基因是 lncRNA AC090377.1。AC090377.1 的通路分析表明，GUCY2F 富集在与视网膜相关的光转导途径中。从单层网络到三层网络，hsa-mir-122 被确定为 ccRCC 发生和进展中的重要分子，为进一步研究 ccRCC 的致癌机制提供了新的策略。
