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Status |
Public on Mar 26, 2024 |
Title |
HOTAIR promotes prostate cancer progression by mediating the interaction between Pol2S2 and CDK9 to maintain transcriptional elongation |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Other
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Summary |
Previous research has predominantly focused on the regulatory role of lncRNA HOTAIR in gene silencing through its interaction with the Polycomb repressive complex 2 (PRC2). Here, our study uncovers a novel regulatory mechanism of HOTAIR, which facilitates prostate cancer (PCa) progression by sustaining transcription elongation. Using ChIRP-seq, RNA-seq, and ChIP-seq, we successfully mapped the binding sites of HOTAIR across the genome and determined their interplay with the epigenetic landscape. We discovered that the co-localization of HOTAIR with the androgen receptor (AR) can activate gene transcription. In the context of AR binding, we discovered that HOTAIR maintains transcription elongation by facilitating the formation of the CDK9/Pol2S2 complex. We revealed a unique capacity of HOTAIR to promote transcriptional activation on gene promoters/bodies with low H3K27me3 enrichment, a function contrasting to its established PRC2-related transcriptional inhibitory roles in regions with high H3K27me3 signal. Finally, we identified two direct target genes of HOTAIR (MMP14 and TNFAIP2), which contribute to the progression of PCa. Collectively, our research sheds new light on HOTAIR's role in transcriptional regulation, offering potential therapeutic strategies and expand our understanding of HOTAIR's roles in PCa progression.
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Overall design |
The project include RNA-seq, ChIRP-seq, ChIP-seq and Cut and Tag between the 22Rv1 WT cells and two HOTAIR poly-A Knock-in cells.
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Contributor(s) |
Qian Y, Lu W |
Citation missing |
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Submission date |
Dec 19, 2022 |
Last update date |
Mar 27, 2024 |
Contact name |
Yuyang Qian |
E-mail(s) |
qyy@nankai.edu.cn
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Organization name |
Nankai university
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Department |
cell and genetic department
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Street address |
94 Weijin Road
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City |
Tianjin |
State/province |
Tianjin |
ZIP/Postal code |
300071 |
Country |
China |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (31)
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Relations |
BioProject |
PRJNA913784 |