Details

Autor(en) / Beteiligte

• Han, Cecil
• Lu, Xiongbin

Titel

Abstract 3080: DBP-RB, a novel RNA-binding protein promotes microRNA processing in the DNA damage response

Ist Teil von

• Cancer research (Chicago, Ill.), 2013-04, Vol.73 (8_Supplement), p.3080-3080

Erscheinungsjahr

2013

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Abstract Defects in the DNA damage response (DDR) and global dysregulation of microRNA (miRNAs) are considered hallmarks of many types of human cancer. Recent studies show that DNA damage such as irradiation, UV and genotoxic agents induce global changes in miRNA expression profile in a variety of cell types. DDR-regulated miRNAs are known to be involved in the initiation and progression of tumorigenesis and also modulate the sensitivity of cells to DNA damaging agents. However, mechanism about how miRNA expression is regulated in response to DNA damage stress is largely unknown. DBP-RB, one of RNA binding protein is known to be overexpressed or amplified in several types of human cancer including neuroblastoma, breast and colon cancer and the biological function of DBP-RB in the cancer is not determined yet. Here, we found that that DBP-RB is interacted with not only Drosha/DGCR8 but also Dicer microprocessors. We also found that DBP-RB is colocalized with DNA damage foci after DNA damage and associated with ATM (Ataxia Telangiectasia Mutated), RAD50 and NBS1 in the DNA damage signaling. DBP-RB knockdown results in increased resistant to genotoxic drugs and inhibition of cell proliferation. We investigated the level of 742 human miRNAs in the DBP-RB knockdown cells and compared with DNA damage induced miRNAs using miRNA quantitative PCR. DBP-RB knockdown cell showed significant changes in the expression levels of a subset of miRNA and in particular, 75% of DBP-RB dependent miRNAs were also regulated in DNA damage-dependent manner. RNA-Immunoprecipitation (IP) reveals that DBP-RB is associated with that specific subset of microRNAs and depletion of DBP-RB inhibits the function of Drosha microprocessor. Taken together, our findings suggest that DBP-RB function as a mediator by transmitting DNA damage signal to the miRNA processors to modulate miRNAs processing through binding Drosha/DGCR8 and Dicer. Citation Format: Cecil Han, Xiongbin Lu. DBP-RB, a novel RNA-binding protein promotes microRNA processing in the DNA damage response. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3080. doi:10.1158/1538-7445.AM2013-3080 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.