ECONOMICS · In cellular conformations of microRNA-34a via magnetic resonance
„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“
- Период
- 2023-01-01 → 2026-04-30
- Финансиране от ЕС
- 206 888 €
- Участници
- 2
- Схема
- HORIZON-TMA-MSCA-PF-EF
Линиите свързват координатора с партньорите.
Накратко на български
Структурата и динамиката на молекулата microRNA-34a се анализират при свързването ѝ с различни генетични мишени, като например гените NOTCH1 и WNT1. Това помага за разработването на по-прецизни лекарства, които да действат само върху конкретни ракови клетки и да намалят страничните ефекти.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Цел на проекта
microRNA-34a (miR-34a) is mis-regulated in ~75% of cancers and is considered a promising drug target. In a recent clinical trial, miR-34a was used against terminal liver cancer showing promising result with remission of 3 patients. However, mortality remained high and was attributed to its ability to target multiple mRNAs. Project ECONOMICS will investigate this issue by elucidating the underlying structure and dynamics of multiple miR-34a:mRNA complexes using NMR spectroscopy and molecular dynamic simulations. This will provide information about the conformation of miR-34a which is mRNA specific. This can further be stabilized by mutations to increase target specificity of miR-34a leading to an improvement in clinical trial results. miR-34a targets and binds the 3’-untranslated-region (3’-UTR) of ~100 mRNAs via the RNA-induced silencing complex, resulting in downregulation of the associated genes. Recently, it was discovered that miR-34a attains a high energy excited state (ES) conformation for mRNA encoding gene SIRT1. Stabilizing this ES resulted in a two-fold increase in gene repression. Can miR-34a have a similar ES for other genes implicated in various cancers? This will be studied by exploring the structure and dynamics of miR-34a when complexed with 3’-UTR of the mRNA encoding the genes HNF4a, NOTCH1, NOTCH2, DLL1 and WNT1. Cellular environment is proposed to affect the ES of miR-34a, therefore a detailed conformational landscape of miR-34a:mRNA complexes will be mapped by comparing both in vitro and in live human cells (cancerous and non-cancerous). This study will provide targeting rules for microRNA within the cell and insight into its regulatory mechanism. This information will improve the efficiency RNA based drug development, giving a competitive edge to EU’s pharmaceutical industry, and ultimately realizing “Europe’s Beating Cancer plan” to achieve long-term survival of 70% patients with cancer by 2035.
Оригинален текст от CORDIS (на английски).
Участници
Връзки
- Виж в CORDIS
- DOI: 10.3030/101067627
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e52ef2212d&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5fd736225&appId=PPGMS
Данни: CORDIS, © Европейски съюз