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Status |
Public on Feb 13, 2023 |
Title |
Estrogen-induced CircRNA, CircPGR, Functions as a CeRNA to Promote Estrogen Receptor-positive Breast Cancer Progression by Regulating Cell Cycle-related Genes |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Non-coding RNA profiling by high throughput sequencing
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Summary |
Estrogen and estrogen receptor (ER)-mediated gene transcriptional events have been well known to be involved in ER-positive breast carcinogenesis. Meanwhile, circular RNAs (circRNAs) are emerging as a new family of functional non-coding RNAs (ncRNAs) with implications in a variety of pathological processes, such as cancer. However, the estrogen-regulated circRNA program and the function of such program remain uncharacterized. Here, genome-wide circRNA profiling by circRNA sequencing (circRNA-seq) revealed tens of thousands of circRNAs were induced by estrogen, and further functional screening for the several circRNAs originated from PGR revealed that one of them, which we named as circPGR, was required for ER-positive breast cancer cell growth and tumorigenesis. CircPGR was found to be localized in the cytosol of cells. Mechanistically, circPGR functioned as a competing endogenous RNA (ceRNA) to sponge miR-301a-5p to regulate the expression of multiple cell cycle genes. The clinical relevance of circPGR was underscored by its high and specific expression in ER-positive breast cancer cell lines and clinical breast cancer tissue samples. Accordingly, siRNA targeting circPGR was proven to be effective in suppressing ER-positive breast cancer cell growth. These findings reveled that, besides the well-known mRNA, microRNA (miRNA), long non-coding RNA (lncRNA) and enhancer RNA (eRNA) programs, estrogen also induced a circRNA program, and exemplified by circPGR, these estrogen-induced circRNAs were required for ER-positive breast cancer cell growth, providing a new class of therapeutic targets for ER-positive breast cancer.
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Overall design |
CircRNA-seq performed in this study was designed to uncover the estrogen-induced circRNA program in MCF7 cells; RNA-seq performed in this study was designed to understand the molecular mechanisms underlying circPGR in gene transcriptional activation.
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Contributor(s) |
Liu W, Wang L, Hu G, Liu YC |
Citation missing |
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Submission date |
Feb 21, 2020 |
Last update date |
Feb 15, 2023 |
Contact name |
Guosheng Hu |
E-mail(s) |
[email protected]
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Phone |
15506972603
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Organization name |
xiamen University
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Department |
School of Pharmaceutical Sciences
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Lab |
liulab
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Street address |
Xiang'an South Road, Xiang'an District
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City |
Xiamen |
State/province |
Fujian |
ZIP/Postal code |
361102 |
Country |
China |
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Platforms (1) |
GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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Samples (4)
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Relations |
BioProject |
PRJNA608011 |
SRA |
SRP250326 |
Supplementary file |
Size |
Download |
File type/resource |
GSE145729_RAW.tar |
314.2 Mb |
(http)(custom) |
TAR (of BIGWIG, TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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