RP11-439C15.4 inhibits the malignant progression of hepatocellular carcinoma via binding to DHX9 and facilitating its
Xuejiao Li1, Zhongying Hu1, Yina Sun2
1Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
Abstract:
Long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and progression of hepatocellular carcinoma (HCC), but the functions and molecular mechanisms of large lncRNAs remain unclear. In this study, HCC data from The Cancer Genome Atlas (TCGA) and 116 HCC cases from our clinical center are used to identify a novel lncRNA, RP11-439C15.4, which is significantly downregulated in HCC. This downregulation is associated with poor prognosis in HCC patients. A series of in vitro and in vivo experiments demonstrate that RP11-439C15.4 significantly inhibits the proliferation, invasion, migration and sorafenib resistance of HCC cells. Further mechanistic investigations reveal that RP11-439C15.4 interacts with DExH-Box Helicase 9 (DHX9) to increase its ubiquitination and accelerate the degradation of DHX9, ultimately suppressing HCC progression. Modulation of DHX9 significantly reverses the effects of RP11-439C15.4 in HCC. In conclusion, this study identifies RP11-439C15.4 as a tumor suppressor and elucidates the regulatory mechanism of the RP11-439C15.4/DHX9 axis in HCC, providing valuable insights into the mechanisms of HCC progression and potential therapeutic targets.
Insights
A novel long noncoding RNA, RP11-439C15.4, is downregulated in hepatocellular carcinoma (HCC). This lncRNA suppresses tumor progression by targeting DHX9, offering potential therapeutic strategies for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are implicated in hepatocellular carcinoma (HCC) development.
- The specific roles and mechanisms of large lncRNAs in HCC remain largely unknown.
- Identifying novel regulatory elements is crucial for understanding HCC progression.
Purpose of the Study:
- To identify and characterize a novel lncRNA involved in HCC.
- To investigate the functional role of this lncRNA in HCC cell behavior.
- To elucidate the molecular mechanism underlying the lncRNA's function in HCC.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) and clinical HCC data.
- In vitro and in vivo experiments to assess cell proliferation, invasion, and migration.
- Co-immunoprecipitation and ubiquitination assays to determine molecular interactions.
- Assessment of sorafenib resistance in HCC cells.
Main Results:
- A novel lncRNA, RP11-439C15.4, was identified and found to be significantly downregulated in HCC.
- Downregulation of RP11-439C15.4 correlates with poor patient prognosis.
- RP11-439C15.4 inhibits HCC cell proliferation, invasion, migration, and enhances sorafenib resistance.
- RP11-439C15.4 interacts with DHX9, promoting its ubiquitination and degradation.
Conclusions:
- RP11-439C15.4 acts as a tumor suppressor in hepatocellular carcinoma.
- The RP11-439C15.4/DHX9 axis plays a critical role in suppressing HCC progression.
- This study provides insights into HCC mechanisms and identifies potential therapeutic targets.
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