Huang Zi-Li, Huang Xiu-Yan, Huang Jin, Huang Xin-Yu, Xu Yong-Hua, Zhou Jian, Tang Zhao-You
Department of General Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Radiology, Xuhui District Central Hospital of Zhongshan Hospital, Fudan University, Shanghai, China.
Front Oncol. 2021 May 18;11:621353. doi: 10.3389/fonc.2021.621353. eCollection 2021.
HCC is one of the most common malignancies with an increasing incidence worldwide, especially in Asian countries. However, even though targeted cancer therapy drugs such as sorafenib and regorafenib are available, the overall outcome of HCC remains unsatisfactory. Thus, it is urgent to investigate the molecular mechanisms of HCC progression, so as to provide accurate diagnostic criteria and therapeutic targets.
RNA-seq data was used to identify and quantify circular RNAs (circRNAs). DESeq2 was used to identify the differentially expressed circRNAs. miRNA binding sites within circRNAs were identified by miRanda. Gene set enrichment analysis (GSEA) was conducted to predict the biological function of circRNAs.
The differential expression analysis identified 107 upregulated and 95 downregulated circRNAs in HCC tissues. We observed that a differentially expressed circRNA (DE-circRNA), hsa_circ_0141900 was highly negatively correlated with its parental gene (PCC < -0.6), which was also closely associated with mTOR signaling pathway. Moreover, we also constructed competing endogenous RNA (ceRNA) network to identify key circRNAs involved in HCC. Notably, hsa_circ_0002130 and hsa_circ_0008774 were highly correlated with the genes involved in gluconeogenesis and HNF3A pathway the target genes, and , suggesting that the two circRNAs might regulate these pathways, respectively. Survival analysis revealed that was associated with favorable prognosis. Furthermore, high expression of hsa_circ_0002130 was found to inhibit tumor cell growth and promotes GOT2 expression.
In summary, the circRNAs highlighted by the integrative analysis greatly improved our understanding of the underlying mechanism of circRNAs in HCC.
肝癌是全球发病率不断上升的最常见恶性肿瘤之一，尤其是在亚洲国家。然而，尽管有索拉非尼和瑞戈非尼等靶向癌症治疗药物，但肝癌的总体治疗效果仍不尽人意。因此，迫切需要研究肝癌进展的分子机制，以提供准确的诊断标准和治疗靶点。
使用RNA测序数据来识别和定量环状RNA（circRNA）。采用DESeq2来识别差异表达的circRNA。通过miRanda识别circRNA中的miRNA结合位点。进行基因集富集分析（GSEA）以预测circRNA的生物学功能。
差异表达分析在肝癌组织中鉴定出107个上调的circRNA和95个下调的circRNA。我们观察到一个差异表达的circRNA（DE-circRNA），即hsa_circ_0141900与其亲本基因高度负相关（PCC < -0.6），其也与mTOR信号通路密切相关。此外，我们还构建了竞争性内源RNA（ceRNA）网络以识别参与肝癌的关键circRNA。值得注意的是，hsa_circ_0002130和hsa_circ_0008774分别与参与糖异生和HNF3A途径的基因高度相关，这表明这两个circRNA可能分别调节这些途径。生存分析显示，[此处原文缺失相关circRNA名称]与良好预后相关。此外，发现hsa_circ_0002130的高表达可抑制肿瘤细胞生长并促进GOT2表达。
总之，综合分析突出的circRNA极大地增进了我们对circRNA在肝癌中潜在机制的理解。
