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Growth arrest-specific 5 (GAS5) is a long non-coding RNA (lncRNA) with diverse functions in regulation of gene expression. Most studies have reported a role for this lncRNA in induction of cell apoptosis and suppression of tumorigenesis process. Although few studies demonstrated up-regulation of this lncRNA in tumor tissues compared to non-tumor tissues of the same origin, the results of in vitro functional studies mostly support the tumor suppressor role for GAS5. A number of recent studies have also shown associations between genomic variants of this gene and risk of cancer in some populations. The role of this lncRNA in modulation of response to anti-cancer regimens has been verified through both in vitro and clinical studies. Taken together, this lncRNA is a putative biomarker and therapeutic target in human malignancies.