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| Status |
Public on Jul 12, 2023 |
| Title |
LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Resistance to endocrine therapy represents a major threat to patients with estrogen receptor α positive (ERα+) breast cancer. The development of resistance is mainly through activating E2F signaling. However, the mechanisms that govern E2F1 activity in these resistant cells remain poorly understood. Here, we identify Actin Gamma 1 Pseudogene 25 (AGPG) as a lncRNA whose expression is driven by epigenomic activation of enhancer in endocrine resistant breast cancer cells. High expression of AGPG is associated with poor survival of ERα+ breast cancer, especially in patients receiving endocrine therapy. Stable knockdown and overexpression of AGPG demonstrate that AGPG promotes endocrine resistance, cell cycle progression, cell proliferation in vitro and in vivo. AGPG functions by direct binding purine rich element binding protein α (PURα), a transcription factor repressing E2F1 signaling and sensitized ERα+ breast cancer cells to endocrine therapy. Via binding to the region responsible for PURα/E2F1 interaction in PURα protein, AGPG releases E2F1 from PURα, leading to activation of E2F1 signaling in ERα+ breast cancer cells. Clinically, E2F1 target genes are strongly correlated with AGPG and PURα expression. Thus, our study reveals AGPG as a promising biomarker and potential therapeutic target in breast cancer.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for MCF7 cells, its knockdown derivatives (shAGPG1, shAGPG2, shPURA1, shPURA2) and derivative with AGPG overexpression(AGPG_OE).
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/37463119/
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| Contributor(s) |
Yu S, Sun H |
| Citation(s) |
37463119 |
| Submission date |
Nov 16, 2022 |
| Last update date |
Oct 14, 2023 |
| Contact name |
Yu Shiyi |
| E-mail(s) |
007585@yzu.edu.cn
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| Phone |
18795899327
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| Organization name |
yangzhou university
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| Street address |
hanjiang district jiangyangzhonglu136, Hanjiang district, Jiangyangzhonglu 136
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| City |
yangzhou |
| State/province |
Jiangsu |
| ZIP/Postal code |
225000 |
| Country |
China |
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| Platforms (1) |
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| Samples (16)
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| GSM6735137 |
MCF7, shAGPG1, rep2 |
| GSM6735138 |
MCF7, shAGPG2, rep1 |
| GSM6735139 |
MCF7, shAGPG2, rep2 |
| GSM6735140 |
MCF7, plvx, rep 1 |
| GSM6735141 |
MCF7, plvx, rep 2 |
| GSM6735142 |
MCF7, plvx_AGPG, rep1 |
| GSM6735143 |
MCF7, plvx_AGPG, rep2 |
| GSM6735144 |
MCF7, shCon_PURA, rep 1 |
| GSM6735145 |
MCF7, shCon_PURA, rep 2 |
| GSM6735146 |
MCF7, shPURA1, rep 1 |
| GSM6735147 |
MCF7, shPURA1, rep 2 |
| GSM6735148 |
MCF7, shPURA2, rep 1 |
| GSM6735149 |
MCF7, shPURA2, rep 2 |
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| Relations |
| BioProject |
PRJNA902381 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE218130_RAW.tar |
3.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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