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

生物 转移 癌症研究 长非编码RNA 核糖核酸 信号转导 肝癌 癌症 基因 细胞生物学 遗传学 肝细胞癌
作者
Kefei Yuan,Jiang Lan,Lin Xu,Xuping Feng,Haotian Liao,Kunlin Xie,Hong Wu,Yong Zeng
出处
期刊:Molecular Cancer [BioMed Central]
卷期号:21 (1) 被引量:51
标识
DOI:10.1186/s12943-022-01578-w
摘要

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.
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