Li Deyuan, Liu Meiliang, Lai Mingshuang, Wang Lijun, Wei Liling, Wu Siqian, Liang Si, Liu Shun, Zeng Xiaoyun
School of public health, Guangxi Medical University, Nanning, Guangxi, China.
Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi, China.
Front Genet. 2025 Apr 15;16:1521360. doi: 10.3389/fgene.2025.1521360. eCollection 2025.
Our previously research has validated the effect of circELMOD3 on HCC tumor inhibition. However, further investigations are warranted to investigate the prognostic significance of circELMOD3 in HCC and its regulation via the competitive endogenous RNA (ceRNA) network.
The gene expression profiles and clinical information were obtained from The Cancer Genome Atlas (TCGA-LIHC) and International Cancer Genome Consortium (ICGC). Base on the circMine, miRWalk and TargetScan database, we constructed circELMOD3-miRNA-mRNA network. Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis was used to constructed the prognostic model. Additionally, Gene set enrichment analysis (GSEA) was conducted for the prognostic-related genes. Finally, the expression levels of genes and proteins were respectively assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.
We constructed a ceRNA network comprising circELMOD3, 5 miRNAs, and 274 mRNAs. From this ceRNA network, we identified four prognostication-relation genes to develop a survival prediction model. In the TCGA-LIHC training set, the area under the curve (AUC) values for one-, three- and five-years of survival were 0.734, 0.718 and 0.707, respectively, then we validated the prognostic model in International Cancer Genome Consortium database. Gene set enrichment analysis displayed that these four prognostic genes were primary enriched pathways related to cell cycle regulation. Our finding demonstrated that circELMOD3 could affect the relative expression levels of N-cadherin, E-cadherin, CDK4, CDK6 and CyclinD1 proteins.
we constructed a novel ceRNA network based on circELMOD3, to comprehensively characterizing the prognosis of HCC, providing valuable insights for the therapy and prognosis of HCC.
我们之前的研究已经证实了circELMOD3对肝癌肿瘤抑制的作用。然而，有必要进一步研究circELMOD3在肝癌中的预后意义及其通过竞争性内源RNA（ceRNA）网络的调控机制。
从癌症基因组图谱（TCGA-LIHC）和国际癌症基因组联盟（ICGC）获取基因表达谱和临床信息。基于circMine、miRWalk和TargetScan数据库，构建circELMOD3-miRNA-mRNA网络。采用单因素Cox和最小绝对收缩和选择算子（LASSO）回归分析构建预后模型。此外，对预后相关基因进行基因集富集分析（GSEA）。最后，分别通过定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹法评估基因和蛋白质的表达水平。
我们构建了一个由circELMOD3、5个miRNA和274个mRNA组成的ceRNA网络。从这个ceRNA网络中，我们鉴定出4个与预后相关的基因来建立生存预测模型。在TCGA-LIHC训练集中，1年、3年和5年生存率的曲线下面积（AUC）值分别为0.734、0.718和0.707，然后我们在国际癌症基因组联盟数据库中验证了该预后模型。基因集富集分析显示，这4个预后基因主要富集在与细胞周期调控相关的通路中。我们的研究结果表明，circELMOD3可以影响N-钙黏蛋白、E-钙黏蛋白、CDK4、CDK6和细胞周期蛋白D1蛋白的相对表达水平。
我们基于circELMOD3构建了一个新的ceRNA网络，以全面表征肝癌的预后，为肝癌的治疗和预后提供有价值的见解。
