长链非编码rna (Long non-coding RNAs, lncRNAs)已被证明在癌症的发生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仍不清楚。

对临床肝癌组织和配对的邻近正常肝组织进行RNA-测序，以鉴定不同表达的lncrna。采用qPCR检测lncrna的表达水平。我们用细胞模型和小鼠模型研究TLNC1在肝癌细胞生长和转移中的作用。采用RNA-seq、RNA下拉结合质谱、RNA免疫沉淀、双荧光素酶报告基因分析和表面等离子体共振分析来分析TLNC1的功能机制。

TLNC1在体内外均能显著促进肝癌细胞的生长和转移。TLNC1通过与TPR相互作用发挥其致瘤作用，诱导TPR介导p53从细胞核转运至细胞质，从而抑制p53靶基因的转录，最终促进肝癌的进展。

Abstract

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 diferentially 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 identifed as a potential tumorigenic lncRNA of liver cancer. TLNC1 signifcantly 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 fnally 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.Keywords: lncRNA, TLNC1, TPR, p53, Liver cancer

原文链接

https://pubmed.ncbi.nlm.nih.gov/35477447/

百度浏览   来源 : 医微客   

版权声明：本网站所有注明来源“医微客”的文字、图片和音视频资料，版权均属于医微客所有，非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源：”医微客”。本网所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，转载仅作观点分享，版权归原作者所有。不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。 本站拥有对此声明的最终解释权。