LINC01116-dependent upregulation of RNA polymerase I transcription drives oncogenic phenotypes in lung adenocarcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.Long noncoding RNA LINC01116 drives lung cancer by enhancing RNA Polymerase I (Pol I) transcription. This oncogenic pathway, regulated by c-Myc, offers a potential therapeutic target for lung adenocarcinoma.
Area Of Science
- Molecular Biology
- Cancer Research
- Genetics
Background
- Hyperactive RNA Polymerase I (Pol I) transcription is a hallmark of cancer, linked to proliferation, poor prognosis, and drug resistance.
- The precise molecular mechanisms driving Pol I hyperactivity in cancer remain largely unknown.
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in gene regulation and cancer development.
Purpose Of The Study
- To investigate the role of lncRNAs in regulating Pol I transcription in lung adenocarcinoma (LUAD).
- To identify specific lncRNAs involved in Pol I hyperactivity and their functional consequences in LUAD.
Main Methods
- Bioinformatics analysis to identify lncRNA candidates interacting with Pol I machinery.
- Fluorescence in situ hybridization and RNA immunoprecipitation to confirm lncRNA localization and interactions.
- Functional assays (knockdown/knock-in, proliferation, apoptosis, migration, invasion) to assess the impact of lncRNAs on LUAD phenotypes and Pol I activity.
Main Results
- Oncogenic LINC01116 was identified as a key regulator, scaffolding Pol I transcription factors (TAF1A, TAF1D) to the rDNA promoter, thereby upregulating Pol I transcription.
- LINC01116-mediated Pol I activation was essential for LUAD cell proliferation, clonogenicity, migration, invasion, and drug resistance.
- The expression of LINC01116 is upregulated by the oncogene c-Myc, establishing a c-Myc-LINC01116-Pol I transcription regulatory feedback loop.
Conclusions
- LINC01116 enhances Pol I transcription by recruiting transcription factors to the rDNA promoter, driving oncogenic activities in LUAD.
- The c-Myc-LINC01116-Pol I transcription axis represents a critical oncogenic pathway in LUAD.
- This pathway presents a potential therapeutic target for modulating Pol I transcription and treating LUAD.
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