Long non-coding RNA GAS5 is critical for maintaining stemness and induces chemoresistance in cancer stem-like cells derived from HCT116

Long non-coding RNAs (lncRNAs) are recognized as critical regulators of self-renewal in human cancer stem-like cells (CSCs), which are a subpopulation of cancer cells primarily responsible for the malignant features of cancer. However, most CSC-related lncRNAs remain unidentified. The results of the present study suggested that growth-arrest-specific transcript 5 (GAS5), a tumor suppressor, exhibited increased expression and was associated with malignant features in human colorectal cancer cell HCT116-derived CSCs. Phenotypic analysis indicated that GAS5 knockdown by specific siRNA significantly decreased CSC self-renewal capacity, proliferation and migration. Moreover, GAS5 knockdown sensitized CSCs to the chemotherapeutic agents 5-fluorouracil and doxorubicin by inducing apoptosis detected by Annexin V-FITC/PI double staining. Inhibition of Nodal growth differentiation factor (NODAL) signaling, which has been reported to be protected by GAS5, presented similar chemosensitivity effects to the GAS5 knockdown results. The present study also assessed the effects of GAS5 overexpression on HCT116 cells, and revealed that overexpression of GAS5 sensitized HCT116 cells to chemotherapeutic agents, which is the opposite of the effect observed in CSCs derived from HCT116 cells. Therefore, it was hypothesized that GAS5 may function as a critical factor for maintaining stemness and that it may exert protective effects on CSCs in a NODAL-dependent manner. Collectively, the results of the present study indicate that GAS5 may be a promising therapeutic target for overcoming malignant features and chemoresistance in colorectal cancer cells.