An LTR Retrotransposon-Derived Long Noncoding RNA lncMER52A Promotes Hepatocellular Carcinoma Progression by Binding p120-Catenin
Published version of a preprint
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.
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The genes with promoter DNA hypomethylation include AFP, several HCC-related lncRNAs (LINC01419, LINC02163, LINC02835), and tumor-associated antigens such as the MAGE gene family.
“These genes included AFP, a diagnostic marker for HCC, several HCC-related lncRNAs (LINC01419, LINC02163, and LINC02835), and tumor-associated antigens such as the MAGE gene family35–37.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [36]
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- Authors
- Wu, Y., Zhao, Y., Huan, L., Zhao, J., Zhou, Y., Xu, L., Hu, Z., Liu, Y., Chen, Z., Wang, L., Huang, S., He, X., & Liang, L.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Fudan University Shanghai Cancer Center (CN)
- ORCID
- Venue
- Cancer Research
- Published
- 2020-03-01
- Volume
- 80
- Issue
- 5
- Pages
- 976-987
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2998098265
- Cited by
- 72
- References
- 0
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 15 · 2023: 7 · 2022: 12 · 2021: 12 · 2020: 10
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81672366, 81972253)
- State Key Project on Infectious Diseases of China (2018ZX10723204)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- long non-coding RNA, LTR retrotransposons, hepatocellular carcinoma, p120 catenin, protein stabilization, Rho GTPases, Rac1, Cdc42, YY1 transcription factor, chromatin accessibility, tumor invasion and metastasis, prognostic factors, therapeutic target
- MeSH terms
- RNA-Seq, Delta Catenin, Female, Carcinoma, Hepatocellular, Humans, Liver, Liver Neoplasms, Male, Middle Aged, Neoplasm Staging, Transcription, Genetic, Biomarkers, Tumor, Signal Transduction, Gene Expression Regulation, Neoplastic, Disease Progression, Retroelements, Terminal Repeat Sequences, cdc42 GTP-Binding Protein, rac1 GTP-Binding Protein, Cell Line, Tumor, YY1 Transcription Factor, Catenins, Protein Stability, RNA, Long Noncoding
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