LncRNA GAS5 enhances radiosensitivity of hepatocellular carcinoma and restricts tumor growth and metastasis by miR-144-5p/ATF2.

Background This study aimed to evaluate the biologic role of growth arrest-specific 5 (GAS5) in radiosensitivity of hepatocellular carcinoma (HCC). Methods The levels of GAS5, miR-144-5p, and activating transcription factor 2 (ATF2) were quantified in HCC tissues and cell lines. RNA immunoprecipitation (RIP) and RNA pull-down assays were used to test the interaction between GAS5 and miR-144-5p. The regulatory relationship between miR-144-5p and ATF2 was identified by the dual-luciferase reporter (DLR) assay. A nude mouse model of HCC was induced to verify the effect of GAS5 on radiosensitivity of HCC in vivo. Results Lower levels of GAS5 and ATF2, and higher levels of miR-144-5p, were found in radiation-resistant human HCC tissues and cell lines. Overexpression of ATF2 or GAS5 enhanced the radiosensitivity of HCC cell lines, while knockdown of ATF2 or GAS5 decreased the radiosensitivity. In addition, GAS5 acted as a miR-144-5p sponge, and miR-144-5p inversely regulated ATF2. Also, GAS5 mediated ATF2 levels through miR-144-5p, and increased the radiosensitivity of HCC by suppressing miR-144-5p both in vivo and in vitro. Conclusion Overexpression of GAS5 upregulates ATF2 through miR-144-5p and is able to enhance the radiosensitivity of HCC.