Fan Tengyang, Jiang Guojun, Shi Rongshu, Yu Ronghua, Xiao Xue, Ke Di
Department of General Medicine, Affiliated Hospital of Zunyi Medical University 149 Dalian Road, Huichuan District, Zunyi 563003, Guizhou, China.
Department of Intervention, Affiliated Hospital of Zunyi Medical University 149 Dalian Road, Huichuan District, Zunyi 563003, Guizhou, China.
Am J Cancer Res. 2022 Apr 15;12(4):1484-1501. eCollection 2022.
Studies have reported that the competing endogenous RNA (ceRNA) networks are related to disease progression and prognosis in patients with hepatocellular carcinoma (HCC). The roles and mechanisms of long-chain non-coding RNA AP003469.4 in HCC have remained unclear. Here, we explored the roles of AP003469.4 in HCC progression using bioinformatics, CCK-8, Transwell assay, etc. AP003469.4 targets miRNAs and these target genes were predicted by the LncBase Predicted v.2, miRDB, miRTarBase, and TargetScan databases. Then, AP003469.4-associated ceRNA network was constructed. Biological functions and mechanisms of differentially expressed genes in the ceRNA network were explored using GO and KEGG. Survival analysis and Cox regression analysis were used to screen prognostic genes and construct a prognostic risk model. The results revealed that AP003469.4, with the area under the curve of 0.9048, was highly expressed in HCC tissues. Increased expression of AP003469.4 was an independent risk factor for the dismal prognosis of HCC patients and was associated with the short overall and disease-free survival. Downregulation of AP003469.4 expression inhibited cell proliferation, cycle transition, invasion, and migration, and promoted cell apoptosis. There were 489 differentially expressed target genes in the ceRNA network, which were involved in several pathways, such as the MAPK signaling pathway, cell cycle, and p53 signaling pathway. The risk model was based on the DTYMK, ZFC3H1, CBX2, PKM, TTC26, ATG10, TAGLN2, CD3EAP, SHISA9, SLC1A5, KPNA2, SCML2, E2F7, and SMARCD1, which were the independent risk factors for poor prognosis of HCC patients. In general, interference with AP003469.4 expression might delay the progression of HCC. AP003469.4 related network could help to identify the hub target molecules in HCC progression, which might be candidate biomarkers for evaluating the prognosis of HCC patients.
研究报告称，竞争性内源性RNA（ceRNA）网络与肝细胞癌（HCC）患者的疾病进展和预后相关。长链非编码RNA AP003469.4在HCC中的作用和机制仍不清楚。在此，我们使用生物信息学、CCK-8、Transwell实验等方法探索了AP003469.4在HCC进展中的作用。AP003469.4靶向miRNA，这些靶基因通过LncBase Predicted v.2、miRDB、miRTarBase和TargetScan数据库进行预测。然后，构建了AP003469.4相关的ceRNA网络。使用GO和KEGG探索ceRNA网络中差异表达基因的生物学功能和机制。采用生存分析和Cox回归分析筛选预后基因并构建预后风险模型。结果显示，AP003469.4在HCC组织中高表达，曲线下面积为0.9048。AP003469.4表达增加是HCC患者预后不良的独立危险因素，与总生存期和无病生存期缩短相关。AP003469.4表达下调抑制细胞增殖、周期转变、侵袭和迁移，并促进细胞凋亡。ceRNA网络中有489个差异表达的靶基因，涉及多个通路，如MAPK信号通路、细胞周期和p53信号通路。风险模型基于DTYMK、ZFC3H1、CBX2、PKM、TTC26、ATG10、TAGLN2、CD3EAP、SHISA9、SLC1A5、KPNA2、SCML2、E2F7和SMARCD1，这些是HCC患者预后不良的独立危险因素。总体而言，干扰AP003469.4表达可能会延缓HCC的进展。AP003469.4相关网络有助于识别HCC进展中的关键靶分子，这可能是评估HCC患者预后的候选生物标志物。
