PSIPCancer · Role of PSIP1 in prostate cancer development and drug resistance
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2021-01-05 → 2023-01-18
- Финансиране от ЕС
- 224 934 €
- Участници
- 1
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Протеинът PSIP1 се изследва за ролята му при предпазване на ДНК от повреди по време на четенето на генетичната информация. Разбирането на този механизъм помага за разработване на нови методи за лечение и подобряване на терапията при рак на простатата.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Role of PSIP1 in prostate cancer development and drug resistance
The focus of the project was on understanding the role of PSIP1, a chromatin factor in transcriptional alteration and maintaining genomic integrity during transcription. PSIP1 is known to have role in transcription elongation, splicing and in HIV integration. But its role in DNA damage repair and genomic instability is not known. Hence, in this project, it aimed to understand the role of this PSIP1 in maintaining genomic integrity during transcription. Understanding the factors that are involved in maintaining genomic integrity is very important and these factors play crucial role in cancer development and treatment response. By modulating such factors, we will be able to develop novel treatment modalities or improving the outcome of existing treatment approaches in cancer. Therefore, this project was aimed at understanding the role of PSIP1 in transcriptional alteration and in maintaining genomic integrity in the sites of transcription. The overall objectives of the project included, studying the altered transcription mediated by PSIP1 through enhancer activation, studying the role of PSIP1 in maintain genome integrity during transcription and the role of PSIP1 in drug resistance in cancer cells. The depletion of PSIP1 resulted in increased R-loops, increased DNA damage leading to reduced synthesis of nascent transcripts at the gene bodies, indicating the novel and important role of PSIP1 in R-loop homeostasis and transcription. This project has also showed the role of PSIP1 in repairing of the DNA damage at the transcribing regions by facilitating homologous repair pathway thereby emphasising its role in transcription. In light of these findings, this project has further demonstrated that the PSIP1 deficient cancers can be targeted better using PARP1 inhibitors and drugs that cause transcription coupled damage.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Understanding the cancer-specific genetic alterations is fundamental to devising novel treatment modalities. This project aims at understanding the role of PSIP1, posterior homeotic domain-containing transcription factors (HOX TFs) and androgen receptor (AR) in transcriptional regulation of prostate cancer cells. These transcriptional regulators are integral to the normal cell homeostasis and are dysregulated in various cancers. Through the preliminary data and analysis, this proposal recognises an interlink between these three factors and the ability of this trio in mediating a cancer-specific transcriptional alteration through activation of cancer-promoting transcriptional enhancers. Using a powerful combination of genome editing, functional genomics and bioinformatics, this proposal aims to discover altered transcriptional programme and its impact on cancer progression and treatment resistance. This project combines the expertise of the researcher in cancer biology with the competences of the host in epigenetics and functional genomics. This project will impart the talented researcher with comprehensive research training in chromatin biology and functional cancer genomics at an elite research Institute, in order to increase his prospects to become an independent research leader. The researcher will also profit from postdoctoral training opportunities in transferable skills available at the host's institution. Completion of the research and training objectives will significantly shape the development of the researcher into an independent leader, assign him a firm place in the European research network
Оригинален текст от CORDIS (на английски).
Участници
- QUEEN MARY UNIVERSITY OF LONDON · LONDONКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз