GAS5 enhances natural killer cell-mediated killing by promoting ubiquitination of SESN2 in prostate cancer cells.

Abstract Background Natural killer (NK) cells mediate the cytotoxicity to prostate cancer (PC) cells. However, the effect of long non-coding RNA (lncRNA) GAS5 on NK cell-mediated killing remains unknown. Methods The expression of GAS5 and SESN2 was compared in isolated NK cells from peripheral blood mononuclear cells (PBMCs) between 42 PC patients and 30 healthy male volunteers. Human NK cell line (NK92 cells) was activated using Interleukin-2 (IL-2). RNA-pull down assay and RNA immunoprecipitation assay were used to elucidate the relationship between GAS5 and SESN2. Calcein-AM release assay and flow cytometry were used to measure the specific lysis rate and cell apoptosis after the co-culture of activated NK92 cells and PC cell lines (PC3 and LNCaP). Results GAS5 was downregulated while SESN2 was upregulated in primary NK cells isolated from PC patients. Knocking down GAS5 in primary NK cells from healthy volunteers suppressed the NK cell-mediated killing to PC cells. In contrast, GAS5 was upregulated in activated NK92 cells. Overexpressing GAS5 in NK92 cells enhanced NK cell-mediated killing to PC cells. The binding between GAS5 and SESN2 promoted the degradation and ubiquitination of SESN2. GAS5 enhanced NK cell-mediated killing to PC cells by promoting ubiquitination of SESN2. Conclusions Our findings demonstrated that GAS5 enhanced NK cell-mediated killing to PC cells by promoting degradation and ubiquitination of SESN2.