|
| Status |
Public on Dec 05, 2019 |
| Title |
RNA-seq analysis of PRMT5-regulated genes in irradiated/non-irradiated LNCaP cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
DNA Double-strand break (DSB) repair is critical for cell survival and genome integrity. Upon recognition of DSBs, repair proteins are transiently upregulated to facilitate repair through homologous recombination (HR) or non-homologous end joining (NHEJ). We present evidence that PRMT5 cooperates with pICln to function as a master epigenetic activator of DNA damage response (DDR) genes involved in HR, NHEJ, and G2 arrest (including RAD51, BRCA1, and BRCA2) to upregulate gene expression upon DNA damage. Contrary to the predominant role of PRMT5 as an epigenetic repressor, our results demonstrate that PRMT5 and pICln can activate gene expression, potentially independent of PRMT5’s obligate cofactor MEP50. Targeting PRMT5 or pICln hinders repair of DSBs in multiple cancer cell lines, and both PRMT5 and pICln expression positively correlates with DDR genes across 32 clinical cancer data sets. Thus, targeting PRMT5 or pICln may be explored in combination with radiation or chemotherapy for cancer treatment.
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| |
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| Overall design |
RNA-seq analysis of both non-irradiated and irradiated LNCaP cells with and without PRMT5 knockdown
|
| Web link |
https://0-doi-org.brum.beds.ac.uk/10.1016/j.isci.2019.100750
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| |
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| Contributor(s) |
Owens JL, Wan J, Hu C |
| Citation(s) |
31884170 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 CA212403 |
Role and targeting of PRMT5 in prostate cancer |
PURDUE UNIVERSITY |
CHANG-DENG HU |
| R01 CA212403 |
Role and targeting of PRMT5 in prostate cancer |
PURDUE UNIVERSITY |
Jiaoti Huang |
| R01 CA212403 |
Role and targeting of PRMT5 in prostate cancer |
PURDUE UNIVERSITY |
Chenglong Li |
| P30 CA023168 |
Cancer Center Support Grant (CORE) Renewal |
PURDUE UNIVERSITY |
TIMOTHY L. RATLIFF |
| P30 CA082709 |
Indiana University Melvin and Bren Simon Cancer Center Support Grant |
INDIANA UNIVERSITY |
PATRICK J. LOEHRER |
| TL1 TR001107 |
Indiana Clinical and Translational Sciences Institute |
INDIANA UNIVERSITY |
Anantha Shekhar |
| UL1 TR001108 |
Indiana Clinical and Translational Sciences Institute |
INDIANA UNIVERSITY |
Anantha Shekhar |
| UL1 TR002529 |
Indiana Clinical and Translational Sciences Institute |
INDIANA UNIVERSITY |
Anantha Shekhar |
|
| Submission date |
Mar 09, 2018 |
| Last update date |
Jan 14, 2020 |
| Contact name |
Chang-Deng Hu |
| E-mail(s) |
hu1@purdue.edu
|
| Organization name |
Purdue University
|
| Department |
Department of Medicinal Chemistry and Molecular Pharmacology
|
| Street address |
201 S. University St, Hansen Life Sciences Building, Room 401A
|
| City |
West Lafayette |
| State/province |
IN |
| ZIP/Postal code |
47907 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (12)
|
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| Relations |
| BioProject |
PRJNA437575 |
| SRA |
SRP134236 |
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