长链非编码 RNA TLNC1 通过抑制 p53 信号通路促进肝癌的生长和转移。

Long noncoding RNA TLNC1 promotes the growth and metastasis of liver cancer via inhibition of p53 signaling.

机构信息

Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.

Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.

出版信息

Mol Cancer. 2022 Apr 27;21(1):105. doi: 10.1186/s12943-022-01578-w.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

背景

长链非编码 RNA（lncRNA）已被证明在癌症的发生和发展中发挥着重要作用。然而，它们在肝癌中的生物学作用和功能机制在很大程度上仍是未知的。

方法

采用 RNA-seq 技术对临床肝癌组织和配对的相邻正常肝组织进行分析，以鉴定差异表达的 lncRNA。qPCR 用于检测 lncRNA 的表达水平。我们通过细胞和小鼠模型研究了 TLNC1 在肝癌细胞生长和转移中的作用。RNA-seq、RNA 下拉结合质谱分析、RNA 免疫沉淀、双荧光素酶报告基因检测和表面等离子体共振分析用于分析 TLNC1 的功能机制。

结果

基于我们自己的 RNA-seq、TCGA RNA-seq 和 TCGA 生存分析数据的交集，TLNC1 被鉴定为肝癌的一种潜在致癌 lncRNA。TLNC1 在体外和体内均显著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运输，从而抑制 p53 靶基因的转录，最终促进肝癌的进展，发挥其致癌功能。