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Table of contents
ACKNOWLEDGEMENTS
ABBREVIATIONS
TABLE OF CONTENTS
INTRODUCTION
Chapter 1. Generalities on long non-coding RNAs
1. History and discovery of lncRNAs
1.1. A role for RNA in the cell: the central dogma of molecular biology
1.2. The first regulatory non-coding RNAs
1.3. From non-coding genome to non-coding transcriptome
2. A general portrait of lncRNA genes and transcripts
2.1. Origin and evolutionary conservation
2.2. Role of lncRNAs in biological diversity
2.3. Coding potential of lncRNA transcripts
2.4. LncRNA transcription and the associated chromatin signature
2.5. Expression pattern of lncRNAs: stability, specificity, and abundance
2.6. Subcellular localization of lncRNAs
3. Classification of lncRNAs
3.1. Classification according to length
3.2. Classification according to genomic location in respect to PCGs
3.3. Classification according to genomic location within specific DNA regulatory elements
3.4. Classification according to lncRNA mechanism of action
3.5. Classification according to associated biological processes
Chapter 2. Long non-coding RNAs as regulators of the epithelial-to-mesenchymal transition.
1. EMT as a driver of metastasis, drug resistance and tumor recurrence
1.1. Generalities on cancer
1.2. EMT as a driver of metastasis and tumor progression
1.3. Molecular basis of the EMT
2. LncRNAs associated with the EMT
2.1. Activators of EMT
2.2. Repressors of EMT
2.3. lncRNAs with controversial roles in EMT
OBJECTIVES
MATERIALS AND METHODS
Chapter 3. Methods
1. In vitro cell model to study EMT
2. CRISPR-based transcriptional activation screening
2.1. Generalities on CRISPR-based screens
2.2. CRISPRa library cloning and phenotypic screening
3. General methods
RESULTS
Chapter 4. A role for HOTAIR in the EMT
1. Introduction
2. Publication n°1
“HOTAIR promotes an epithelial-to-mesenchymal transition through relocation of the histone demethylase Lsd1.”
Chapter 5. Functional discovery of novel lncRNAs in the EMT
1. Introduction 95
2. Publication n°2
“CRISPRa screen of chromatin-enriched lncRNAs reveals a new regulator of epithelial identity.”
3. Additional data
3.1. CRISPRa-screening of invasion-associated lncRNAs
3.2. MAL-1 knock-down using siRNAs
3.3. Transcriptomic analysis of MAL-1 overexpression
DISCUSSION
Chapter 6. Discussion
1. Cyto- and Chro-seq as a tool to study the non-coding transcriptome
2. The role of lncRNAs in the epithelial-to-mesenchymal transition
2.1. HOTAIR as a modulator of Lsd1 function
2.2. MAL-1, a novel lncRNA repressor of epithelial identity
2.3. lncRNAs as regulators of epithelial plasticity
REFERENCES


