Study of the control of gene expression lncRNA INXS involved in the apoptosis

• Grant number: 15/00324-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2015
• End date: August 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Sergio Verjovski Almeida
• Grantee: Alexandre Videira
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 14/03620-2 - Characterization of the mechanisms of action of long non-coding RNAs involved with gene activation programs in human cells, AP.TEM

Abstract

The discovery of countless long non-coding RNA (lncRNAs, > 200 nucleotides) transcripts in the human genome dramatically altered our understanding of cell biology, especially the mechanisms involved in the process of programmed cell death. Apoptosis is a plenty regulated process that plays an essential role in the development and tissue homeostasis. The dysregulation of natural defense mechanism promote aberrant cell proliferation and accumulation of genetic mutations, resulting in tumorigenesis, and often confers resistance to drugs for cancer cells. A complex network of signaling pathway acts to promote or inhibit apoptosis in response to various intra- and extracellular stimuli, and between the flags are alternative splicing of the transcript BCL-X (BCL-2 family member) which gives the product anti-apoptotic BCL-XL, and pro-apoptotic BCL-XS. Our studies found that the lncRNA INXS is mediator of the splicing, leading to the formation of BCL-XS and causing apoptosis, and showed that INXS had reduced expression in various types of tumors, which is consistent with the fact that tumor cells are more resistant to cell death. Lack determine the factors that cause this reduction in INXS expression in tumors. For this, in this project we will featuers the minimal promoter INXS using reporter assay and we will featuers transcription factors that bind the promoter region of INXS between different cell types using pull-down proteins that bind to INXS followed by western -blot and / or mass spectrometry. Functional characterization of the promoter will provide an understanding of the mechanisms that lead to transcription lncRNA INXS. In addition, we will evaluate the specific allele expression using smFISH, which provide an understanding of the coordinated expression of INXS and BCL-X, involving the promoter and changes in chromatin. This study will advance the possible exploitation of lncRNA INXS as a target in cancer therapy. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VIDEIRA, ALEXANDRE; BECKEDORFF, FELIPE C.; DASILVA, LUCAS F.; VERJOVSKI-ALMEIDA, SERGIO. PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors. CELL COMMUNICATION AND SIGNALING, v. 19, n. 1, JAN 11 2021. (15/00324-6, 18/23693-5, 12/12005-4, 14/03620-2)

VIDEIRA, ALEXANDRE; BECKEDORFF, FELIPE C.; DASILVA, LUCAS F.; VERJOVSKI-ALMEIDA, SERGIO. PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors. CELL COMMUNICATION AND SIGNALING, v. 19, n. 1, p. 16-pg., 2021-01-11. (12/12005-4, 18/23693-5, 15/00324-6, 14/03620-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

VIDEIRA, Alexandre. Effect of lincRNA PVT1 associated with Enhancer of Zeste homolog 2 (EZH2) and with androgen receptor (AR) on the large-scale gene expression in LNCaP prostate cancer cells. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.