ArticleHepatology (Baltimore, Md.)2019
Lnc-UCID Promotes G1/S Transition and Hepatoma Growth by Preventing DHX9-Mediated CDK6 Down-regulation.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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77 citing papers in PubMed, 105 citations in OpenAlex.
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- Development of a Dual Gene-Targeted Multi-Sirna with Branched Structure and Its Role in the Therapy of Liver Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Integrative Transcriptome-Wide Association Study With Expression Quantitative Trait Loci Colocalization Identifies a Causal VAMP8 Variant for Nasopharyngeal Carcinoma Susceptibility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- HBV-associated hepatocellular carcinomas inhibit antitumor CD8Nature communications · 2025Article
- LINC01094 promotes gastric cancer through dual targeting of CDKN1A by directly binding RBMS2 and HDAC1.Biology direct · 2024Article
- Deciphering the nexus between long non-coding RNAs and endoplasmic reticulum stress in hepatocellular carcinoma: biomarker discovery and therapeutic horizons.Cell death discovery · 2024Review
- Prognostic Value of an Immune Long Non-Coding RNA Signature in Liver Hepatocellular Carcinoma.Journal of microbiology and biotechnology · 2024Article
- cAMP-phosphodiesterase 4D7 (PDE4D7) forms a cAMP signalosome complex with DHX9 and is implicated in prostate cancer progression.Molecular oncology · 2024Article
- LncRNA XXYLT1-AS2 promotes tumor progression via autophagy inhibition through ubiquitinated degradation of TFEB in hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- What are the changes in the hotspots and frontiers of microRNAs in hepatocellular carcinoma over the past decade?World journal of clinical oncology · 2024Article
- Clinical Significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 and MicroRNA Axis in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Article
- Role of Non-Coding RNAs in Hepatocellular Carcinoma Progression: From Classic to Novel Clinicopathogenetic Implications.Cancers · 2023Review
- Bioinformatics prediction and experimental verification identify cuproptosis-related lncRNA as prognosis biomarkers of hepatocellular carcinoma.Biochemistry and biophysics reports · 2023Article
- ETS-1-activated LINC01016 over-expression promotes tumor progression via suppression of RFFL-mediated DHX9 ubiquitination degradation in breast cancers.Cell death & disease · 2023Article
- Long non-coding RNA HIF1A-As2 and MYC form a double-positive feedback loop to promote cell proliferation and metastasis in KRAS-driven non-small cell lung cancer.Cell death and differentiation · 2023Article
- LINC00998-encoded micropeptide SMIM30 promotes the G1/S transition of cell cycle by regulating cytosolic calcium level.Molecular oncology · 2023Article
- Phosphorylation of UHRF2 affects malignant phenotypes of HCC and HBV replication by blocking DHX9 ubiquitylation.Cell death discovery · 2023Article
- A novel NSUN5/ENO3 pathway promotes the Warburg effect and cell growth in clear cell renal cell carcinoma by 5-methylcytosine-stabilized ENO3 mRNA.American journal of translational research · 2023Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
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Abstract
Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a limited number of them have been functionally characterized. Here, we identified an oncogenic lncRNA, named lnc-UCID (lncRNA up-regulating CDK6 by interacting with DHX9). Lnc-UCID was up-regulated in hepatocellular carcinoma (HCC), and a higher lnc-UCID level was correlated with shorter recurrence-free survival of HCC patients. Both gain-of-function and loss-of function studies revealed that lnc-UCID enhanced cyclin-dependent kinase 6 (CDK6) expression and thereby promoted G1/S transition and cell proliferation. Studies from mouse xenograft models revealed that tumors derived from lnc-UCID-silenced HCC cells had a much smaller size than those from control cells, and intratumoral injection of lnc-UCID small interfering RNA suppressed xenograft growth. Mechanistically, the 850-1030-nt domain of lnc-UCID interacted physically with DEAH (Asp-Glu-Ala-His) box helicase 9 (DHX9), an RNA helicase. On the other hand, DHX9 post-transcriptionally suppressed CDK6 expression by binding to the 3'-untranslated region (3'UTR) of CDK6 mRNA. Further investigation disclosed that lnc-UCID enhanced CDK6 expression by competitively binding to DHX9 and sequestering DHX9 from CDK6-3'UTR. In an attempt to explore the mechanisms responsible for lnc-UCID up-regulation in HCC, we found that the lnc-UCID gene was frequently amplified in HCC. Furthermore, miR-148a, whose down-regulation was associated with an increase of lnc-UCID in HCC, could bind lnc-UCID and inhibit its expression. Conclusion: Up-regulation of lnc-UCID, which may result from amplification of its gene locus and down-regulation of miR-148a, can promote HCC growth by preventing the interaction of DHX9 with CDK6 and subsequently enhancing CDK6 expression. These findings provide insights into the biological functions of lncRNAs, the regulatory network of cell cycle control, and the mechanisms of HCC development, which may be exploited for anticancer therapy.
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