Abstract
The ongoing discovery of long noncoding RNA (lncRNA) involvement in carcinogenesis prevention and development has made significant strides in breast cancer therapeutics. lncRNA growth arrest-specific 5 (GAS5) is downregulated in breast cancer, and its downregulation is linked to advanced clinical staging and grading as well as poor survival outcomes. The apoptosis modality is the most sought-after cell death modality in cancer therapeutics and a major challenge to the current treatment paradigm is drug resistance. This review examines GAS5 as a therapeutic target and an inducer of apoptosis through various mechanisms, including the role of GAS5-derived small nucleolar RNAs (snoRNAs) in the prevention of carcinogenesis, GAS5 as a microRNA (miRNA) sponge, thereby upregulating several tumor suppressors that promote apoptosis. Moreover, GAS5 is a riborepressor of the glucocorticoid receptor, hindering inhibitors of apoptosis. Additionally, GAS5 sensitizes breast cancer to radiotherapy, chemotherapy and endocrine therapy and alleviates drug resistance either directly through overexpression or indirectly through the administration of drugs that increase its expression, consequently promoting apoptosis. GAS5 is involved in various crucial signaling pathways in breast cancer, such as the PI3K/AKT/mTOR, Wnt/β-catenin, and NF-κB pathways and is itself regulated by many pathways. Recognized as a potent tumor suppressor, GAS5 presents a compelling opportunity for more profound research as a potential game-changing therapeutic target in breast cancer.