The role of POLR1D, a common subunit of RNA polymerases I and III in colorectal cancer

The role of POLR1D, a common subunit of RNA polymerases I and III in colorectal cancer
Project leader: Dr Damian Graczyk
Duration: 2018-01-01 / 2022-06-30
Budget: 2 892 366 PLN
Contribution from European Funds: 100%

Objectives
Colorectal cancer (CRC) is a major cause of morbidity and mortality. The level of POLR1D, a common subunit of RNA polymerases I and III, is elevated in CRC cells. The aim of this project is to assess whether a gene
encoding POLR1D is a colorectal cancer oncogene. We will determine whether increased levels of POLR1D contribute to the tumourigenic characteristics of colorectal cancer cells and elucidate the mechanism of this
phenomenon. Finding new molecular pathways that sustain tumour cell growth will help to better understand the pathogenesis of CRC and provide potential novel target(s) to treat this disease.

Predicted outcome of the project
Overall, the proposed project will assess whether POLR1D is a colorectal cancer oncogene. Furthermore, the project will provide a mechanistic explanation to how overexpression of POLR1D increases tumourigenic
properties of CRC cancer cells. We will elucidate whether POLR1D changes Pol I/III-dependent transcription and/or POLR1D has a new transcription-independent role. If the latter is the case, we will provide a mechanistic
insight into this phenomenon. As Pol I and Pol III play a significant role in numerous diseases, including cancer, deciphering the mechanisms of their regulation is of great importance. Given the fact that new therapies are badly needed to treat CRC, our results may identify a novel therapeutic target in this fatal disease. The data obtained during the course of the project will be disseminated by publishing in scientific highimpact journals and by presenting at scientific conferences. We also plan to launch a lab-specific web-site to communicate our scientific interests and to report the progress of our research.