Genomics

Dataset Information

0

NanoStrong miRNA from DU145 CF and HF cells


ABSTRACT: NanoString duplicate runs were created for CF- and HF-resistant cells, and for matched parental duplicate samples corresponding to each radioresistant cell type. Prostate cancer is the second most common cause of cancer death in men, and radiotherapy is a standard curative therapy for localized disease. Unfortunately, aggressive radioresistant relapses can arise, and the molecular underpinnings of radioresistance are unknown. Modern clinical radiotherapy is evolving to deliver higher doses of radiation in fewer fractions (hypofractionation). We therefore analyzed genomic, transcriptomic and proteomic data to characterize the determinants of prostate cancer radioresistance in cells treated with both conventionally fractionated and hypofractionated radiotherapy. Independent of fractionation schedule, resistance to radiotherapy involved massive genomic instability and abrogation of DNA mismatch repair. Specific prostate cancer driver genes were modulated at the RNA and protein levels, with distinct protein subcellular responses to radiotherapy. Conventional fractionation led to a far more aggressive biomolecular response than hypofractionation. Testing pre-clinical candidates identified in cell lines, we revealed POLQ as a radiosensitizer. POLQ-modulated radioresistance in model systems and was predictive of it in large patient cohorts. Pharmacologic and genetic inhibition of POLQ re-sensitized radioresistant cells, creating signatures seen in primary patient cohorts. The molecular response to radiation is highly multi-modal, and sheds light on prostate cancer lethality.

ORGANISM(S): Homo sapiens

PROVIDER: GSE241078 | GEO | 2024/08/24

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2022-08-18 | PXD020303 | Pride
2018-10-04 | GSE120798 | GEO
2024-01-26 | PXD034360 | Pride
2014-09-27 | E-GEOD-61816 | biostudies-arrayexpress
2014-09-27 | E-GEOD-61620 | biostudies-arrayexpress
2014-09-27 | E-GEOD-61772 | biostudies-arrayexpress
2019-12-31 | PXD012922 | Pride
2020-07-08 | GSE149988 | GEO
2024-07-31 | PXD052368 | Pride
2019-06-25 | PXD007188 | Pride