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

被引:57
作者
Yuan, Kefei [1 ,2 ,3 ]
Lan, Jiang [3 ]
Xu, Lin [3 ]
Feng, Xuping [3 ]
Liao, Haotian [1 ,2 ]
Xie, Kunlin [1 ,2 ]
Wu, Hong [1 ,2 ,3 ]
Zeng, Yong [1 ,2 ,3 ]
机构
[1] Sichuan Univ, West China Hosp, Dept Liver Surg Liver Transplantat, State Key Lab Biotherapy & Canc Ctr, Chengdu 610041, Peoples R China
[2] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China
[3] Sichuan Univ, West China Hosp, Lab Liver Surg, Chengdu 610041, Peoples R China
关键词
lncRNA; TLNC1; TPR; p53; Liver cancer; LNCRNA; EXPORT;
D O I
10.1186/s12943-022-01578-w
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:17
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