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Cancer Res ; 80(5): 976-987, 2020 03 01.
Article in English | MEDLINE | ID: mdl-31874857

ABSTRACT

Long terminal repeat (LTR) retrotransposons are a major class of transposable elements, accounting for 8.67% of the human genome. LTRs can serve as regulatory sequences and drive transcription of tissue or cancer-specific transcripts. However, the role of these LTR-activated transcripts, especially long non-coding RNAs (lncRNA), in cancer development remains largely unexplored. Here, we identified a novel lncRNA derived from MER52A retrotransposons (lncMER52A) that was exclusively expressed in hepatocellular carcinoma (HCC). HCC patients with higher lncMER52A had advanced TNM stage, less differentiated tumors, and shorter overall survival. LncMER52A promoted invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, lncMER52A stabilized p120-catenin and triggered the activation of Rho GTPase downstream of p120-catenin. Furthermore, we found that chromatin accessibility was crucial for the expression of lncMER52A. In addition, YY1 transcription factor bound to the cryptic MER52A LTR promoter and drove lncMER52A transcription in HCC. In conclusion, we identified an LTR-activated lncMER52A, which promoted the progression of HCC cells via stabilizing p120-catenin and activating p120-ctn/Rac1/Cdc42 axis. LncMER52A could serve as biomarker and therapeutic target for patients with HCC. SIGNIFICANCE: A novel long noncoding RNA lncMER52 modulates cell migration and invasion via posttranslational control of p120-catenin protein stability. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/5/976/F1.large.jpg.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/genetics , Catenins/genetics , Liver Neoplasms/genetics , RNA, Long Noncoding/metabolism , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Humans , Liver/pathology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Protein Stability , RNA, Long Noncoding/genetics , RNA-Seq , Retroelements/genetics , Signal Transduction/genetics , Terminal Repeat Sequences/genetics , Transcription, Genetic , YY1 Transcription Factor/metabolism , cdc42 GTP-Binding Protein/metabolism , rac1 GTP-Binding Protein/metabolism , Delta Catenin
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