Simple SummaryLong non-coding RNAs (lncRNAs) are a large class of RNA molecules known to regulate the expression of genes. Although expressed in a highly tissue-specific manner, they appear to modulate virtually all pathways in the cell, either in normal or disease states. LncRNAs are often aberrantly expressed in cancers and can act as oncogenes or tumor suppressors. Here, we describe various mechanisms by which lncRNAs influence gene expression as they bind other RNAs, genomic DNA, or proteins. Particularly, we discuss their relationship with transcription factors as they act on pathways relevant to cancer. While much remains to be discovered about how they regulate genes, lncRNAs hold great therapeutic potential, especially in their transcription factor interactions.AbstractAs a group of diseases characterized by uncontrollable cell growth, cancer is highly multifaceted in how it overrides checkpoints controlling proliferation. Amongst the regulators of these checkpoints, long non-coding RNAs (lncRNAs) can have key roles in why natural biological processes go haywire. LncRNAs represent a large class of regulatory transcripts that can localize anywhere in cells. They were found to affect gene expression on many levels from transcription to mRNA translation and even protein stability. LncRNA participation in such control mechanisms can depend on cell context, with given transcripts sometimes acting as oncogenes or tumor suppressors. Importantly, the tissue-specificity and low expression levels of lncRNAs make them attractive therapeutic targets or biomarkers. Here, we review the various cellular processes affected by lncRNAs and outline molecular strategies they use to control gene expression, particularly in cancer and in relation to transcription factors.