Analysis of the transcriptional regulation mechanisms mediated by the lincRNA PVT1 in a prostate cancer model

• Grant number: 22/11192-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2023
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sergio Verjovski Almeida
• Grantee: Fábio Nunes de Mello
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 18/23693-5 - Mechanisms of action of long non-coding RNAs involved with gene activation programs in eukaryotes, AP.TEM

Abstract

The development of prostate cancer is knowingly dependent on the presence of the androgen hormone, with the androgen receptor (AR) acting in regulating the transcription of hundreds of genes involved with oncogenic transformation. However, little is known about the exact mechanisms of this regulation. It has been demonstrated several long intergenic non-coding RNAs (lincRNAs) can associate with AR, recruiting chromatin remodeling enzymes and directing their activity within the genome, but few of these lincRNAs have been completely characterized, specially in genomic scales. Following previous works of our laboratory, we have focused on the lincRNA PVT1, an oncogene whose overexpression is observed in several cancer types, but whose oncogenic mechanism remains uncharacterized. For this, we have developed a knockdown model for PVT1 in a prostate cancer lineage, and we aim to evaluate the impact of the reduced PVT1 expression on chromatin markers and regulatory proteins across the genome. Furthermore, we intend to analyse the effects of the knockdown and androgen hormone presence on the cell´s transcriptome, aiming to correlate the observed epigenetic marks and changes in gene expression induced by the association of PVT1 and AR, in order to characterize their oncogenic mechanisms in prostate cancer.