Functional characterization of the PVT1 lincRNA associated with androgen receptor in prostate Cancer

• Grant number: 21/13698-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2022
• Effective date (End): September 09, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Maria Gabriela Berzoti Coelho
• Grantee: Gabriel Nakanishi Fortes
• 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

Prostate Cancer (PCa) is second cancer most diagnosed and the lead cause of death cancer-related in men. The development of PCa is highly dependent on the androgen receptor (AR), a transcription factor that modulates the effect of androgenic hormones and the transcription of genes in prostatic cells, promoting their activation or inhibition. Once the androgen receptor plays an essential role in PCa, androgen deprivation therapy can suppress PCa. However, AR can modificate in order to keep itself activated even on hormonal privation conditions. Long non-coding RNAs (lncRNAs) are nucleic acids with 200 or more nucleotides associated with cancer development since their regulation seems to impact cell functions like proliferation, apoptosis, and induction of metastasis. We have previously reported that lncRNA PVT1 is associated with AR in the PCa cells LNCaP, suggesting PVT1 is involved in a repressive transcriptional program androgen-dependent, leading to the expression inhibition of tumor suppressor genes. Therefore, this study aims to investigate the cellular mechanisms that are affected by PVT1 in prostatic cancer. After silencing the lncRNA PVT1 on cell lines of PCa (LNCAP, VCaP, and DU-145) cultivated in androgenic hormone absence or presence, the cellular processes of apoptosis, proliferation, and invasion will be evaluated. The results will allow a better understanding of the pathology and progression of PCa, as well as the description of a new and potential pharmacological target.(AU)