Long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in cancer development and progression. However, their biological roles and function mechanisms in liver cancer remain largely unknown. RNA-seq was performed with clinical hepatoma tissues and paired adjacent normal liver tissues to identify differentially expressed lncRNAs. qPCR was utilized to examine the expression levels of lncRNAs. We studied the function of TLNC1 in cell growth and metastasis of hepatoma with both cell and mouse models. RNA-seq, RNA pull-down coupled with mass spectrometry, RNA immunoprecipitation, dual luciferase reporter assay, and surface plasmon resonance analysis were used to analyze the functional mechanism of TLNC1. Based on the intersection of our own RNA-seq, TCGA RNA-seq, and TCGA survival analysis data, TLNC1 was identified as a potential tumorigenic lncRNA of liver cancer. TLNC1 significantly enhanced the growth and metastasis of hepatoma cells both in vitro and in vivo. TLNC1 exerted its tumorigenic function through interaction with TPR and inducing the TPR-mediated transportation of p53 from nucleus to cytoplasm, thus repressing the transcription of p53 target genes and finally contributing to the progression of liver cancer. TLNC1 is a promising prognostic factor of liver cancer, and the TLNC1-TPR-p53 axis can serve as a potential therapeutic target for hepatoma treatment.

中文翻译：

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长链非编码RNA TLNC1通过抑制p53信号促进肝癌的生长和转移

长链非编码 RNA (lncRNA) 已被证明在癌症发展和进展中发挥重要作用。然而，它们在肝癌中的生物学作用和功能机制仍然很大程度上未知。使用临床肝癌组织和配对的相邻正常肝组织进行 RNA-seq，以鉴定差异表达的 lncRNA。qPCR 用于检查 lncRNA 的表达水平。我们用细胞模型和小鼠模型研究了 TLNC1 在肝癌细胞生长和转移中的作用。RNA-seq、RNA pull-down耦合质谱、RNA免疫沉淀、双荧光素酶报告基因分析和表面等离子共振分析用于分析TLNC1的功能机制。基于我们自己的 RNA-seq、TCGA RNA-seq 和 TCGA 生存分析数据的交集，TLNC1被鉴定为肝癌潜在的致瘤lncRNA。TLNC1在体外和体内均显着增强肝癌细胞的生长和转移。TLNC1通过与TPR相互作用并诱导TPR介导的p53从细胞核到细胞质的转运发挥其致瘤功能，从而抑制p53靶基因的转录，最终促进肝癌的进展。TLNC1是一种很有前景的肝癌预后因子，TLNC1-TPR-p53轴可作为肝癌治疗的潜在治疗靶点。TLNC1通过与TPR相互作用并诱导TPR介导的p53从细胞核到细胞质的转运发挥其致瘤功能，从而抑制p53靶基因的转录，最终促进肝癌的进展。TLNC1是一种很有前景的肝癌预后因子，TLNC1-TPR-p53轴可作为肝癌治疗的潜在治疗靶点。TLNC1通过与TPR相互作用并诱导TPR介导的p53从细胞核到细胞质的转运发挥其致瘤功能，从而抑制p53靶基因的转录，最终促进肝癌的进展。TLNC1是一种很有前景的肝癌预后因子，TLNC1-TPR-p53轴可作为肝癌治疗的潜在治疗靶点。