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Status |
Public on Aug 31, 2022 |
Title |
HMGN5 escorts oncogenic STAT3 signaling by regulating chromatin landscape in tumorigenesis of breast cancer |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
Epigenetic alterations are widely linked with carcinogenesis, therefore becoming emerging therapeutic targets in the treatment of cancers, including breast cancer. HMGNs are nucleosome binding proteins, which regulate chromatin structures in a cell type- and disease-specific manner. However, the roles of HMGNs in the tumorigenesis of breast cancer are less known. In this study, we report that HMGNs are highly expressed in 3D-cultured breast cancer cells. HMGN5, a member of HMGNs, controls the proliferation, invasion and metastasis of breast cancer cells in vitro and in vivo. Clinically, HMGN5 is an unfavorable prognostic marker in patients. Mechanistically, HMGN5 is governed by active STAT3 transcriptionally and further escorts STAT3 to shape oncogenic chromatin landscape and transcriptional program. Lastly, we provide evidence that interference of HMGN5 by nanoparticle-packaged siRNA is potentially an effective approach in breast cancer treatment. Taken together, our findings reveal a novel feed-forward circuit between HMGN5 and STAT3 in promoting breast cancer tumorigenesis and suggest HMGN5 as a novel epigenetic therapeutic target in STAT3-hyperactive breast cancer.
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Overall design |
MDA-MB-231 cells are transfected with control siRNA (NC) or siRNA targeting STAT3 (siSTAT3) or HMGN5 (siHMGN5) to examine the transcriptome and genomic histone H3K27ac alteration upon STAT3 or HMGN5 depletion. In the second experiment, siSTAT3 cells are further infected with lentiviral vector or HMGN5 to detect the effect of ectopic HMGN5 on the transcriptome in siSTAT3 cells
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Contributor(s) |
Jiahui M, Meijun H, Hanqi X, Chaochen W |
Citation(s) |
36066963 |
Submission date |
Jan 12, 2022 |
Last update date |
Nov 30, 2022 |
Contact name |
Chaochen Wang |
E-mail(s) |
chaochenwang@intl.zju.edu.cn
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Organization name |
Zhejiang University
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Department |
ZJU-UoE Institute
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Street address |
718 East Haizhou Rd
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City |
Haining |
ZIP/Postal code |
314400 |
Country |
China |
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Platforms (2) |
GPL23227 |
BGISEQ-500 (Homo sapiens) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (19)
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Relations |
BioProject |
PRJNA796499 |
Supplementary file |
Size |
Download |
File type/resource |
GSE193507_RAW.tar |
379.1 Mb |
(http)(custom) |
TAR (of BEDGRAPH, TXT) |
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Raw data are available in SRA |
Processed data provided as supplementary file |
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