Repression of lncRNA NEAT1 enhances the antitumor activity of CD8+T cells against hepatocellular carcinoma via regulating miR-155/Tim-3

Background: Immunotherapy is a promising method for the treatment of hepatocellular carcinoma (HCC), in which CD8+T cells play a key role. The influence of long noncoding RNA (lncRNA) nuclear-enriched autosomal transcript 1(NEAT1) on the antitumor activity of CD8+T cells was clarified in this study. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from HCC patients, and the expressions of NEAT1 and Tim-3 were determined by qRT-PCR and western blot, respectively. CD8+T cell apoptosis and cell percentage were analyzed via flow cytometry. The cytolysis activity of CD8+T cells against HCC cells was examined. RNA immunoprecipitation (RIP) and RNA pull-down assay were performed to explore the interaction between NEAT1 and miR-155. Results: NEAT1 and Tim-3 were up-regulated in the PBMCs of patients with HCC (n = 20) compared with healthy subjects (n = 20). Down-regulation of NEAT1 restrained CD8+T cell apoptosis and enhanced the cytolysis activity, while interference of miR-155 showed the opposite effects by up-regulating Tim-3. Binding and interaction between NEAT1 and miR-155 were validated in CD8+T cells. Down-regulation of NEAT1 restrained CD8+T cell apoptosis and enhanced the cytolysis activity through the miR-155/Tim-3 pathway. Repression of NEAT1 suppressed tumor growth in HCC mice. Conclusion: Via modulating the miR-155/Tim-3 pathway, repression of NEAT1 restrained CD8+T cell apoptosis and enhanced the cytolysis activity against HCC, implying an effective target for improving the outcome of immunotherapy.